Amylin: Pharmacology, physiology, and clinical potential

Pharmacological Reviews

Volumn 67, Issue 3, 2015, Pages 564-600

  Hay, Debbie L ^a   Chen, Steve ^b   Lutz, Thomas A ^c   Parkes, David G ^b   Roth, Jonathan D ^d  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b AMYLIN PHARMACEUTICALS INC   (United States)

^c UNIVERSITY OF ZURICH   (Switzerland)

^d INTERCEPT PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLIN; AMYLIN RECEPTOR; AMYLIN RECEPTOR AGONIST; ANOREXIGENIC AGENT; CALCITONIN[8-32][30 ASPARAGINE 32 TYROSINAMIDE]; CHOLECYSTOKININ; DAVALINTIDE; ESTRADIOL; FENFLURAMINE; GLUCAGON LIKE PEPTIDE 1; GUANINE NUCLEOTIDE BINDING PROTEIN; LEPTIN; LIRAGLUTIDE; LORCASERIN; MACROGOL; MELANOCORTIN; METRELEPTIN; PEPTIDE YY [3-36]; PHENTERMINE; PRAMLINTIDE; RECEPTOR SUBTYPE; SIBUTRAMINE; ANTIDIABETIC AGENT;

ALZHEIMER DISEASE; AREA POSTREMA; BODY WEIGHT; CENTRAL NERVOUS SYSTEM; CIRCUMVENTRICULAR ORGAN; CONTROLLED CLINICAL TRIAL (TOPIC); DIABETES MELLITUS; DIET INDUCED OBESITY; DIURESIS; ENERGY EXPENDITURE; ENERGY METABOLISM; FAT MASS; FOOD INTAKE; GENE OVEREXPRESSION; GENETIC MODEL; GLYCEMIC CONTROL; HORMONE ACTION; HORMONE DEFICIENCY; HORMONE METABOLISM; HORMONE RECEPTOR INTERACTION; HORMONE RELEASE; HUMAN; HYPERGLUCAGONEMIA; IMMOBILIZATION STRESS; INSULIN DEPENDENT DIABETES MELLITUS; INTRACELLULAR SIGNALING; LIPOLYSIS; MATERNAL BEHAVIOR; NATRIURESIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PHASE 2 CLINICAL TRIAL (TOPIC); PLASMA CLEARANCE; PLASMA HALF LIFE; POSTPRANDIAL STATE; PREPULSE INHIBITION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS INHIBITION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SATIETY; STOMACH EMPTYING; WEIGHT REDUCTION; ANIMAL; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; METABOLISM; PHYSIOLOGY;

ANIMALS; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; ENERGY METABOLISM; HUMANS; HYPOGLYCEMIC AGENTS; ISLET AMYLOID POLYPEPTIDE; WEIGHT LOSS;

EID: 84952638764     PISSN: 00316997     EISSN: 15210081     Source Type: Journal    
DOI: 10.1124/pr.115.010629     Document Type: Review

References (304)

1. Abedini A and Schmidt AM (2013) Mechanisms of islet amyloidosis toxicity in type 2 diabetes. FEBS Lett 587:1119–1127.
2. Adler BL, Yarchoan M, Hwang HM, Louneva N, Blair JA, Palm R, Smith MA, Lee HG, Arnold SE, and Casadesus G (2014) Neuroprotective effects of the amylin analogue pramlintide on Alzheimer’s disease pathogenesis and cognition. Neurobiol Aging 35:793–801.
3. Alexander SP, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, Peters JA, and Harmar AJ; CGTP Collaborators (2013) The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors. Br J Pharmacol 170: 1459–1581.
4. Andreassen KV, Hjuler ST, Furness SG, Sexton PM, Christopoulos A, Nosjean O, Karsdal MA, and Henriksen K (2014) Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias. PLoS ONE 9:e92042.
5. Archbold JK, Flanagan JU, Watkins HA, Gingell JJ, and Hay DL (2011) Structural insights into RAMP modification of secretin family G protein-coupled receptors: implications for drug development. Trends Pharmacol Sci 32:591–600.
6. Armour SL, Foord S, Kenakin T, and Chen WJ (1999) Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor. J Pharmacol Toxicol Methods 42:217–224.
7. Arnelo U, Permert J, Adrian TE, Larsson J, Westermark P, and Reidelberger RD (1996) Chronic infusion of islet amyloid polypeptide causes anorexia in rats. Am J Physiol 271:R1654–R1659.
8. Aronne L, Fujioka K, Aroda V, Chen K, Halseth A, Kesty NC, Burns C, Lush CW, and Weyer C (2007) Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebocontrolled, dose-escalation study. J Clin Endocrinol Metab 92:2977–2983.
9. Aronne LJ, Halseth AE, Burns CM, Miller S, and Shen LZ (2010) Enhanced weight loss following coadministration of pramlintide with sibutramine or phentermine in a multicenter trial. Obesity (Silver Spring) 18:1739–1746.
10. Asarian L, Boyle CN, and Lutz TA (2011) Estradiol (E2) increases the acute eatinginhibitory effect of amylin in ovariectomized (OVX) rats. Appetite 57 (Supplement 1):S2.
11. Asarian L, Eckel LA, and Geary N (1998) Behaviorally specific inhibition of sham feeding by amylin. Peptides 19:1711–1718.
12. Asarian L and Geary N (2006) Modulation of appetite by gonadal steroid hormones. Philos Trans R Soc Lond B Biol Sci 361:1251–1263.
13. Asmar M, Bache M, Knop FK, Madsbad S, and Holst JJ (2010) Do the actions of glucagon-like peptide-1 on gastric emptying, appetite, and food intake involve release of amylin in humans? J Clin Endocrinol Metab 95:2367–2375.
14. Bailey RJ, Walker CS, Ferner AH, Loomes KM, Prijic G, Halim A, Whiting L, Phillips ARJ, and Hay DL (2012) Pharmacological characterization of rat amylin receptors: implications for the identification of amylin receptor subtypes. Br J Pharmacol 166:151–167.
15. Baisley SK, Bremer QZ, Bakshi VP, and Baldo BA (2014) Antipsychotic-like actions of the satiety peptide, amylin, in ventral striatal regions marked by overlapping calcitonin receptor and RAMP-1 gene expression. J Neurosci 34:4318–4325.
16. Baldo BA and Kelley AE (2001) Amylin infusion into rat nucleus accumbens potently depresses motor activity and ingestive behavior. Am J Physiol Regul Integr Comp Physiol 281:R1232–R1242.
17. Banks WA (2006) The blood-brain barrier as a regulatory interface in the gut-brain axes. Physiol Behav 89:472–476.
18. Banks WA and Kastin AJ (1998) Differential permeability of the blood-brain barrier to two pancreatic peptides: insulin and amylin. Peptides 19:883–889.
19. Banks WA, Kastin AJ, Maness LM, Huang W, and Jaspan JB (1995) Permeability of the blood-brain barrier to amylin. Life Sci 57:1993–2001.
20. Barrachina MD, Martínez V, Wang L, Wei JY, and Taché Y (1997) Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice. Proc Natl Acad Sci USA 94:10455–10460.
21. Barth SW, Riediger T, Lutz TA, and Rechkemmer G (2004) Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat. Brain Res 997:97–102.
22. Beaumont K, Kenney MA, Young AA, and Rink TJ (1993) High affinity amylin binding sites in rat brain. Mol Pharmacol 44:493–497.
23. Becskei C, Grabler V, Edwards GL, Riediger T, and Lutz TA (2007) Lesion of the lateral parabrachial nucleus attenuates the anorectic effect of peripheral amylin and CCK. Brain Res 1162:76–84.
24. Becskei C, Riediger T, Zünd D, Wookey P, and Lutz TA (2004) Immunohistochemical mapping of calcitonin receptors in the adult rat brain. Brain Res 1030:221–233.
25. Beglinger S, Meyer-Gerspach AC, Graf S, Zumsteg U, Drewe J, Beglinger C, and Gutzwiller JP (2014) Effect of a test meal on meal responses of satiation hormones and their association to insulin resistance in obese adolescents. Obesity (Silver Spring) 22:2047–2052.
26. Bell D and McDermott BJ (1995) Activity of amylin at CGRP1-preferring receptors coupled to positive contractile response in rat ventricular cardiomyocytes. Regul Pept 60:125–133.
27. Bello NT, Kemm MH, Ofeldt EM, and Moran TH (2010) Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates. Am J Physiol Regul Integr Comp Physiol 299: R945–R952.
28. Bhavsar S, Watkins J, and Young A (1998) Synergy between amylin and cholecystokinin for inhibition of food intake in mice. Physiol Behav 64:557–561.
29. Bhogal R, Smith DM, and Bloom SR (1992) Investigation and characterization of binding sites for islet amyloid polypeptide in rat membranes. Endocrinology 130: 906–913.
30. Blackard WG, Clore JN, and Kellum JM (1994) Amylin/insulin secretory ratios in morbidly obese man: inverse relationship with glucose disappearance rate. J Clin Endocrinol Metab 78:1257–1260.
31. Bomberger JM, Parameswaran N, Hall CS, Aiyar N, and Spielman WS (2005a) Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking. J Biol Chem 280:9297–9307.
32. Bomberger JM, Spielman WS, Hall CS, Weinman EJ, and Parameswaran N (2005b) Receptor activity-modifying protein (RAMP) isoform-specific regulation of adrenomedullin receptor trafficking by NHERF-1. J Biol Chem 280:23926–23935.
33. Booe JM, Walker CS, Barwell J, Kuteyi G, Simms J, Bill RM, Harris PW, Brimble MA, Poyner DR, and Hay DL, et al. (2015) Structural basis for receptor activitymodifying protein-dependent selective peptide recognition by a G protein-coupled receptor. Mol Cell, in press.
34. Bouali SM, Wimalawansa SJ, and Jolicoeur FB (1995) In vivo central actions of rat amylin. Regul Pept 56:167–174.
35. Bouizar Z, Rostène WH, and Milhaud G (1987) Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidenced by autoradiography. Proc Natl Acad Sci USA 84:5125–5128.
36. Boyle CN and Lutz TA (2011) Amylinergic control of food intake in lean and obese rodents. Physiol Behav 105:129–137.
37. Boyle CN, Rossier MM, and Lutz TA (2010) Diet-induced obesity, hyperamylinemia and amylin sensitivity. Appetite 54:636.
38. Boyle CN, Rossier MM, and Lutz TA (2011) Influence of high-fat feeding, dietinduced obesity, and hyperamylinemia on the sensitivity to acute amylin. Physiol Behav 104:20–28.
39. Brown LM and Clegg DJ (2010) Central effects of estradiol in the regulation of food intake, body weight, and adiposity. J Steroid Biochem Mol Biol 122:65–73.
40. Butera PC (2010) Estradiol and the control of food intake. Physiol Behav 99:175–180.
41. Butler AE, Jang J, Gurlo T, Carty MD, Soeller WC, and Butler PC (2004) Diabetes due to a progressive defect in beta-cell mass in rats transgenic for human islet amyloid polypeptide (HIP Rat): a new model for type 2 diabetes. Diabetes 53: 1509–1516.
42. Castagné V, Moser PC, and Porsolt RD (2009) Preclinical behavioral models for predicting antipsychotic activity. Adv Pharmacol 57:381–418.
43. Chance WT, Balasubramaniam A, Zhang FS, Wimalawansa SJ, and Fischer JE (1991) Anorexia following the intrahypothalamic administration of amylin. Brain Res 539:352–354.
44. Chapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Lush CW, Chen K, Lacerte C, Burns C, and McKay R, et al. (2007) Low-dose pramlintide reduced food intake and meal duration in healthy, normal-weight subjects. Obesity (Silver Spring) 15:1179–1186.
45. Chapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Strobel S, Wang Y, Burns C, Lush C, and Weyer C, et al. (2005) Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes. Diabetologia 48: 838–848.
46. Christopoulos A, Christopoulos G, Morfis M, Udawela M, Laburthe M, Couvineau A, Kuwasako K, Tilakaratne N, and Sexton PM (2003) Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem 278:3293–3297.
47. Christopoulos G, Paxinos G, Huang XF, Beaumont K, Toga AW, and Sexton PM (1995) Comparative distribution of receptors for amylin and the related peptides calcitonin gene related peptide and calcitonin in rat and monkey brain. Can J Physiol Pharmacol 73:1037–1041.
48. Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, Main MJ, Foord SM, and Sexton PM (1999) Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol 56:235–242.
49. Clapper JR, Athanacio J, Wittmer C, Griffin PS, D’Souza L, Parkes DG, and Roth JD (2013) Effects of amylin and bupropion/naltrexone on food intake and body weight are interactive in rodent models. Eur J Pharmacol 698:292–298.
50. Clodi M, Thomaseth K, Pacini G, Hermann K, Kautzky-Willer A, Waldhüsl W, Prager R, and Ludvik B (1998) Distribution and kinetics of amylin in humans. Am J Physiol 274:E903–E908.
51. Colburn WA, Gottlieb AB, Koda J, and Kolterman OG (1996) Pharmacokinetics and pharmacodynamics of AC137 (25,28,29 tripro-amylin, human) after intravenous bolus and infusion doses in patients with insulin-dependent diabetes. J Clin Pharmacol 36:13–24.
52. Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, and Reid KB (1987) Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci USA 84:8628–8632.
53. Cooper GJS, Leighton B, Dimitriadis GD, Parry-Billings M, Kowalchuk JM, Howland K, Rothbard JB, Willis AC, and Reid KBM (1988) Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc Natl Acad Sci USA 85:7763–7766.
54. Cornish J, Callon KE, King AR, Cooper GJ, and Reid IR (1998) Systemic administration of amylin increases bone mass, linear growth, and adiposity in adult male mice. Am J Physiol 275:E694–E699.
55. Covasa M, Marcuson JK, and Ritter RC (2001) Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin. Am J Physiol Regul Integr Comp Physiol 280:R331–R337.
56. Crawley JN and Beinfeld MC (1983) Rapid development of tolerance to the behavioural actions of cholecystokinin. Nature 302:703–706.
57. Dackor R, Fritz-Six K, Smithies O, and Caron K (2007) Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. J Biol Chem 282:18094–18099.
58. Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA, Goldring SR, Gebre- Medhin S, Galson DL, Zajac JD, and Karsenty G (2004) Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J Cell Biol 164:509–514.
59. Davey RA, Turner AG, McManus JF, Chiu WS, Tjahyono F, Moore AJ, Atkins GJ, Anderson PH, Ma C, and Glatt V, et al. (2008) Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice. J Bone Miner Res 23: 1182–1193.
60. Deacon CF and Ahrén B (2011) Physiology of incretins in health and disease. Rev Diabet Stud 8:293–306.
61. Dhillo WS, Small CJ, Jethwa PH, Russell SH, Gardiner JV, Bewick GA, Seth A, Murphy KG, Ghatei MA, and Bloom SR (2003) Paraventricular nucleus administration of calcitonin gene-related peptide inhibits food intake and stimulates the hypothalamo-pituitary-adrenal axis. Endocrinology 144:1420–1425.
62. Dobolyi A (2009) Central amylin expression and its induction in rat dams. J Neurochem 111:1490–1500.
63. Edvinsson L and Warfvinge K (2013) CGRP receptor antagonism and migraine therapy. Curr Protein Pept Sci 14:386–392.
64. Eftekhari S and Edvinsson L (2011) Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level. BMC Neurosci 12:112.
65. Eiden S, Daniel C, Steinbrueck A, Schmidt I, and Simon E (2002) Salmon calcitonin - a potent inhibitor of food intake in states of impaired leptin signalling in laboratory rodents. J Physiol 541:1041–1048.
66. Enoki S, Mitsukawa T, Takemura J, Nakazato M, Aburaya J, Toshimori H, and Matsukara S (1992) Plasma islet amyloid polypeptide levels in obesity, impaired glucose tolerance and non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 15:97–102.
67. Fang J, Landersdorfer CB, Cirincione B, and Jusko WJ (2013) Study reanalysis using a mechanism-based pharmacokinetic/pharmacodynamic model of pramlintide in subjects with type 1 diabetes. AAPS J 15:15–29.
68. Feigh M, Andreassen KV, Neutzsky-Wulff AV, Petersen ST, Hansen C, Bay-Jensen AC, Henriksen JE, Beck-Nielsen H, Christiansen C, and Henriksen K, et al. (2012) Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic betacell area and function in Zucker diabetic fatty rats. Br J Pharmacol 167:151–163.
69. Feigh M, Henriksen K, Andreassen KV, Hansen C, Henriksen JE, Beck-Nielsen H, Christiansen C, and Karsdal MA (2011) A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats. Diabetes Obes Metab 13:911–920.
70. Fernandes-Santos C, Zhang Z, Morgan DA, Guo DF, Russo AF, and Rahmouni K (2013) Amylin acts in the central nervous system to increase sympathetic nerve activity. Endocrinology 154:2481–2488.
71. Fidler MC, Sanchez M, Raether B, Weissman NJ, Smith SR, Shanahan WR, and Anderson CM; BLOSSOM Clinical Trial Group (2011) A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 96:3067–3077.
72. Fineman MS, Koda JE, Shen LZ, Strobel SA, Maggs DG, Weyer C, and Kolterman OG (2002) The human amylin analog, pramlintide, corrects postprandial hyperglucagonemia in patients with type 1 diabetes. Metabolism 51:636–641.
73. Flood JF and Morley JE (1992) Differential effects of amylin on memory processing using peripheral and central routes of administration. Peptides 13:577–580.
74. Fry M, Hoyda TD, and Ferguson AV (2007) Making sense of it: roles of the sensory circumventricular organs in feeding and regulation of energy homeostasis. Exp Biol Med (Maywood) 232:14–26.
75. Fukuda T, Hirai Y, Maezawa H, Kitagawa Y, and Funahashi M (2013) Electrophysiologically identified presynaptic mechanisms underlying amylinergic modulation of area postrema neuronal excitability in rat brain slices. Brain Res 1494: 9–16.
76. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, and Day WW (2011) Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 377: 1341–1352.
77. Geary N (2005) A new way of looking at eating. Am J Physiol Regul Integr Comp Physiol 288:R1444–R1446.
78. Gebre-Medhin S, Mulder H, Pekny M, Westermark G, Törnell J, Westermark P, Sundler F, Ahrén B, and Betsholtz C (1998a) Increased insulin secretion and glucose tolerance in mice lacking islet amyloid polypeptide (amylin). Biochem Biophys Res Commun 250:271–277.
79. Gebre-Medhin S, Mulder H, Zhang Y, Sundler F, and Betsholtz C (1998b) Reduced nociceptive behavior in islet amyloid polypeptide (amylin) knockout mice. Brain Res Mol Brain Res 63:180–183.
80. Gedulin BR, Jodka CM, Herrmann K, and Young AA (2006) Role of endogenous amylin in glucagon secretion and gastric emptying in rats demonstrated with the selective antagonist, AC187. Regul Pept 137:121–127.
81. Gedulin BR, Rink TJ, and Young AA (1997) Dose-response for glucagonostatic effect of amylin in rats. Metabolism 46:67–70.
82. Gedulin BR and Young AA (1998) Hypoglycemia overrides amylin-mediated regulation of gastric emptying in rats. Diabetes 47:93–97.
83. Gingell JJ, Burns ER, and Hay DL (2014) Activity of pramlintide, rat and human amylin but not Ab1-42 at human amylin receptors. Endocrinology 155:21–26.
84. Gingell JJ, Qi T, Bailey RJ, and Hay DL (2010) A key role for tryptophan 84 in receptor activity-modifying protein 1 in the amylin 1 receptor. Peptides 31: 1400–1404.
85. Gloy VL, Lutz TA, Langhans W, Geary N, and Hillebrand JJ (2010) Basal plasma levels of insulin, leptin, ghrelin, and amylin do not signal adiposity in rats recovering from forced overweight. Endocrinology 151:4280–4288.
86. Grabler V and Lutz TA (2004) Chronic infusion of the amylin antagonist AC 187 increases feeding in Zucker fa/fa rats but not in lean controls. Physiol Behav 81: 481–488.
87. Grandt D, Schimiczek M, Beglinger C, Layer P, Goebell H, Eysselein VE, and Reeve JR Jr (1994) Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept 51:151–159.
88. Granneman JG and Stricker EM (1984) Food intake and gastric emptying in rats with streptozotocin-induced diabetes. Am J Physiol 247:R1054–R1061.
89. Green GM, Guan D, Schwartz JG, and Phillips WT (1997) Accelerated gastric emptying of glucose in Zucker type 2 diabetic rats: role in postprandial hyperglycaemia. Diabetologia 40:136–142.
90. Guerreiro LH, Guterres MF, Melo-Ferreira B, Erthal LC, Rosa MdaS, Lourenço D, Tinoco P, and Lima LM (2013) Preparation and characterization of PEGylated amylin. AAPS PharmSciTech 14:1083–1097.
91. Gutierrez-Rojas I, Lozano D, Nuche-Berenguer B, Moreno P, Acitores A, Ramos- Alvarez I, Rovira A, Novials A, Martin-Crespo E, Villanueva-Penacarrillo ML, et al. (2013) Amylin exerts osteogenic actions with different efficacy depending on the diabetic status. Mol Cell Endocrinol 365:309–315.
92. Halford JC, Wanninayake SC, and Blundell JE (1998) Behavioral satiety sequence (BSS) for the diagnosis of drug action on food intake. Pharmacol Biochem Behav 61: 159–168.
93. Hanabusa T, Kubo K, Oki C, Nakano Y, Okai K, Sanke T, and Nanjo K (1992) Islet amyloid polypeptide (IAPP) secretion from islet cells and its plasma concentration in patients with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 15:89–96.
94. Hansen TK, Schaffer L, and Lau J (2007) inventors, Novo Nordisk A/S, assignee. Amylin derivatives. US Patent 20090099085. 2007 Mar 15.
95. Harikumar KG, Simms J, Christopoulos G, Sexton PM, and Miller LJ (2009) Molecular basis of association of receptor activity-modifying protein 3 with the family B G protein-coupled secretin receptor. Biochemistry 48:11773–11785.
96. Harris PJ, Cooper ME, Hiranyachattada S, Berka JL, Kelly DJ, Nobes M, and Wookey PJ (1997) Amylin stimulates proximal tubular sodium transport and cell proliferation in the rat kidney. Am J Physiol 272:F13–F21.
97. Hassan K and Heptulla RA (2009) Reducing postprandial hyperglycemia with adjuvant premeal pramlintide and postmeal insulin in children with type 1 diabetes mellitus. Pediatr Diabetes 10:264–268.
98. Hay DL, Christopoulos G, Christopoulos A, Poyner DR, and Sexton PM (2005) Pharmacological discrimination of calcitonin receptor: receptor activity-modifying protein complexes. Mol Pharmacol 67:1655–1665.
99. Hay DL, Harris PW, Kowalczyk R, Brimble MA, Rathbone DL, Barwell J, Conner AC, and Poyner DR (2014) Structure-activity relationships of the N-terminus of calcitonin gene-related peptide: key roles of alanine-5 and threonine-6 in receptor activation. Br J Pharmacol 171:415–426.
100. Hay DL, Poyner DR, and Quirion R; International Union of Pharmacology (2008) International Union of Pharmacology. LXIX. Status of the calcitonin gene-related peptide subtype 2 receptor. Pharmacol Rev 60:143–145.
101. Heptulla RA, Rodriguez LM, Mason KJ, and Haymond MW (2009) Twenty-four-hour simultaneous subcutaneous Basal-bolus administration of insulin and amylin in adolescents with type 1 diabetes decreases postprandial hyperglycemia. J Clin Endocrinol Metab 94:1608–1611.
102. Hilton JM, Chai SY, and Sexton PM (1995) In vitro autoradiographic localization of the calcitonin receptor isoforms, C1a and C1b, in rat brain. Neuroscience 69: 1223–1237.
103. Hilton JM, Dowton M, Houssami S, and Sexton PM (2000) Identification of key components in the irreversibility of salmon calcitonin binding to calcitonin receptors. J Endocrinol 166:213–226.
104. Hollander P, Maggs DG, Ruggles JA, Fineman M, Shen L, Kolterman OG, and Weyer C (2004) Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obes Res 12:661–668.
105. Holst JJ (2004) Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors. Expert Opin Emerg Drugs 9:155–166.
106. Horcajada-Molteni MN, Chanteranne B, Lebecque P, Davicco MJ, Coxam V, Young A, and Barlet JP (2001) Amylin and bone metabolism in streptozotocin-induced diabetic rats. J Bone Miner Res 16:958–965.
107. Horcajada-Molteni MN, Davicco MJ, Lebecque P, Coxam V, Young AA, and Barlet JP (2000) Amylin inhibits ovariectomy-induced bone loss in rats. J Endocrinol 165: 663–668.
108. Horowitz M and Fraser R (1994) Disordered gastric motor function in diabetes mellitus. Diabetologia 37:543–551.
109. Hoyda TD, Smith PM, and Ferguson AV (2009) Gastrointestinal hormone actions in the central regulation of energy metabolism: potential sensory roles for the circumventricular organs. Int J Obes (Lond) 33 (Suppl 1):S16–S21.
110. Huang X, Yang J, Chang JK, and Dun NJ (2010) Amylin suppresses acetic acidinduced visceral pain and spinal c-fos expression in the mouse. Neuroscience 165: 1429–1438.
111. Huffman DM, McLean GW, and Seagrove MA (2009) Continuous subcutaneous pramlintide infusion therapy in patients with type 1 diabetes: observations from a pilot study. Endocr Pract 15:689–695.
112. Hwang JJ, Chan JL, Ntali G, Malkova D, and Mantzoros CS (2008) Leptin does not directly regulate the pancreatic hormones amylin and pancreatic polypeptide: interventional studies in humans. Diabetes Care 31:945–951.
113. Isaksson B, Wang F, Permert J, Olsson M, Fruin B, Herrington MK, Enochsson L, Erlanson-Albertsson C, and Arnelo U (2005) Chronically administered islet amyloid polypeptide in rats serves as an adiposity inhibitor and regulates energy homeostasis. Pancreatology 5:29–36.
114. Jacobsen SH, Olesen SC, Dirksen C, Jørgensen NB, Bojsen-Møller KN, Kielgast U, Worm D, Almdal T, Naver LS, and Hvolris LE, et al. (2012) Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obes Surg 22:1084–1096.
115. Jagger C, Chambers T, and Pondel M (2000) Transgenic mice reveal novel sites of calcitonin receptor gene expression during development. Biochem Biophys Res Commun 274:124–129.
116. Janes S, Gaeta L, Beaumont K, Beeley N, and Rink T (1996) The selection of pramlintide for clinical evaluation (Abstract). Diabetes 45 (Suppl 2):235A.
117. Jones KL, Horowitz M, Carney BI, Wishart JM, Guha S, and Green L (1996) Gastric emptying in early noninsulin-dependent diabetes mellitus. J Nucl Med 37: 1643–1648.
118. Kadmiel M, Fritz-Six K, and Caron K (2012) Understanding RAMPs through genetically engineered mouse models. Adv Exp Med Biol 744:49–60.
119. Kadmiel M, Fritz-Six K, Pacharne S, Richards GO, Li M, Skerry TM, and Caron KM (2011) Research resource: Haploinsufficiency of receptor activity-modifying protein-2 (RAMP2) causes reduced fertility, hyperprolactinemia, skeletal abnormalities, and endocrine dysfunction in mice. Mol Endocrinol 25:1244–1253.
120. Kanatsuka A, Makino H, Ohsawa H, Tokuyama Y, Yamaguchi T, Yoshida S, and Adachi M (1989) Secretion of islet amyloid polypeptide in response to glucose. FEBS Lett 259:199–201.
121. Karsdal MA, Henriksen K, Bay-Jensen AC, Molloy B, Arnold M, John MR, Byrjalsen I, Azria M, Riis BJ, and Qvist P, et al. (2011) Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials. J Clin Pharmacol 51:460–471.
122. Kautzky-Willer A, Thomaseth K, Pacini G, Clodi M, Ludvik B, Streli C, Waldhäusl W, and Prager R (1994) Role of islet amyloid polypeptide secretion in insulinresistant humans. Diabetologia 37:188–194.
123. Kaygisiz Z, Ozden H, Erkasap N, Koken T, Gunduz T, Ikizler M, and Kural T (2010) Positive inotropic, positive chronotropic and coronary vasodilatory effects of rat amylin: mechanisms of amylin-induced positive inotropy. Acta Physiol Hung 97: 362–374.
124. Keller J, Catala-Lehnen P, Huebner AK, Jeschke A, Heckt T, Lueth A, Krause M, Koehne T, Albers J, and Schulze J, et al. (2014) Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Nat Commun 5:5215.
125. Kelley AE (1999) Functional specificity of ventral striatal compartments in appetitive behaviors. Ann N Y Acad Sci 877:71–90.
126. Kim GW, Lin JE, Blomain ES, and Waldman SA (2013) New advances in models and strategies for developing anti-obesity drugs. Expert Opin Drug Discov 8:655–671.
127. King AB (2009) Minimal reduction in insulin dosage with pramlintide therapy when pretreatment near-normal glycemia is established and square-wave meal bolus is used. Endocr Pract 15:229–233.
128. King AB (2010) Comparison of the post-meal glucose response to different insulin bolus waveforms in insulin pump- and pre-meal pramlintide-treated type 1 diabetes patients. Diabetes Technol Ther 12:105–108.
129. Klopfenstein BK, Krisky C, Rooney W, and Purnell JQ (2010) Amygdala activation by leptin predicts food intake in lean men. Obesity (Silver Spring) 18 (Suppl 1):76.
130. Knight ZA, Hannan KS, Greenberg ML, and Friedman JM (2010) Hyperleptinemia is required for the development of leptin resistance. PLoS ONE 5:e11376.
131. Kong MF, King P, Macdonald IA, Stubbs TA, Perkins AC, Blackshaw PE, Moyses C, and Tattersall RB (1997) Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM. Diabetologia 40:82–88.
132. Kong MF, Stubbs TA, King P, Macdonald IA, Lambourne JE, Blackshaw PE, Perkins AC, and Tattersall RB (1998) The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM. Diabetologia 41:577–583.
133. Kowalczyk R, Brimble MA, Tomabechi Y, Fairbanks AJ, Fletcher M, and Hay DL (2014) Convergent chemoenzymatic synthesis of a library of glycosylated analogues of pramlintide: structure-activity relationships for amylin receptor agonism. Org Biomol Chem 12:8142–8151.
134. Le Foll C, Johnson MD, Dunn-Meynell AA, Boyle CN, Lutz TA, and Levin BE (2015) Amylin-induced central IL-6 production enhances ventromedial hypothalamic leptin signaling. Diabetes 64:1621–1631.
135. Ladenheim EE (2015) Liraglutide and obesity: a review of the data so far. Drug Des Devel Ther 9:1867–1875.
136. Leckström A, Björklund K, Permert J, Larsson R, and Westermark P (1997) Renal elimination of islet amyloid polypeptide. Biochem Biophys Res Commun 239: 265–268.
137. Lee HJ, Choe YH, Lee JH, Sohn YB, Kim SJ, Park SW, Son JS, Kim SW, and Jin DK (2011) Delayed response of amylin levels after an oral glucose challenge in children with Prader-Willi syndrome. Yonsei Med J 52:257–262.
138. Leinung MC and Grasso P (2012) [D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, augments the effects of orally delivered exenatide and pramlintide acetate on energy balance and glycemic control in insulin-resistant male C57BLK/6-m db/db mice. Regul Pept 179:33–38.
139. Lenhart PM, Broselid S, Barrick CJ, Leeb-Lundberg LMF, and Caron KM (2013) G-protein-coupled receptor 30 interacts with receptor activity-modifying protein 3 and confers sex-dependent cardioprotection. J Mol Endocrinol 51:191–202.
140. Levetan C, Want LL, Weyer C, Strobel SA, Crean J, Wang Y, Maggs DG, Kolterman OG, Chandran M, and Mudaliar SR, et al. (2003) Impact of pramlintide on glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions among patients with type 1 diabetes intensively treated with insulin pumps. Diabetes Care 26:1–8.
141. Levin BE and Dunn-Meynell AA (2000) Defense of body weight against chronic caloric restriction in obesity-prone and -resistant rats. Am J Physiol Regul Integr Comp Physiol 278:R231–R237.
142. Ludvik B, Lell B, Hartter E, Schnack C, and Prager R (1991) Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes. Diabetes 40:1615–1619.
143. Lupien JR and Young AA (1993) No measurable effect of amylin on lipolysis in either white or brown isolated adipocytes from rats. Diabetes Nutr Metab 6:13–18.
144. Luttrell LM (2006) Transmembrane signaling by G protein-coupled receptors. Methods Mol Biol 332:3–49.
145. Lutz TA (2006) Amylinergic control of food intake. Physiol Behav 89:465–471.
146. Lutz TA (2010) The role of amylin in the control of energy homeostasis. Am J Physiol Regul Integr Comp Physiol 298:R1475–R1484.
147. Lutz TA (2012a) Control of energy homeostasis by amylin. Cell Mol Life Sci 69: 1947–1965.
148. Lutz TA (2012b) Effects of amylin on eating and adiposity. Handb Exp Pharmacol 209:231–250.
149. Lutz TA, Althaus J, Rossi R, and Scharrer E (1998a) Anorectic effect of amylin is not transmitted by capsaicin-sensitive nerve fibers. Am J Physiol 274:R1777–R1782.
150. Lutz TA, Del Prete E, and Scharrer E (1994) Reduction of food intake in rats by intraperitoneal injection of low doses of amylin. Physiol Behav 55:891–895.
151. Lutz TA, Del Prete E, and Scharrer E (1995a) Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin. Peptides 16:457–462.
152. Lutz TA and Geary N (2008) Gastrointestinal factors in appetite and food research - animal research, in Appetite and Food Intake: Behavioral and Physiological Consideration (Harris R, ed) pp 163–186, CRC Press, Boca Raton, FL.
153. Lutz TA, Geary N, Szabady MM, Del Prete E, and Scharrer E (1995b) Amylin decreases meal size in rats. Physiol Behav 58:1197–1202.
154. Lutz TA, Mollet A, Rushing PA, Riediger T, and Scharrer E (2001) The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/ nucleus of the solitary tract (AP/NTS) lesioned rats. Int J Obes Relat Metab Disord 25:1005–1011.
155. Lutz TA, Rossi R, Althaus J, Del Prete E, and Scharrer E (1997) Evidence for a physiological role of central calcitonin gene-related peptide (CGRP) receptors in the control of food intake in rats. Neurosci Lett 230:159–162.
156. Lutz TA, Rossi R, Althaus J, Del Prete E, and Scharrer E (1998b) Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats. Peptides 19:1533–1540.
157. Lutz TA, Senn M, Althaus J, Del Prete E, Ehrensperger F, and Scharrer E (1998c) Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats. Peptides 19:309–317.
158. Lutz TA, Tschudy S, Rushing PA, and Scharrer E (2000) Attenuation of the anorectic effects of cholecystokinin and bombesin by the specific amylin antagonist AC 253. Physiol Behav 70:533–536.
159. Ma J, Rayner CK, Jones KL, and Horowitz M (2009) Insulin secretion in healthy subjects and patients with Type 2 diabetes—role of the gastrointestinal tract. Best Pract Res Clin Endocrinol Metab 23:413–424.
160. Mack C, Wilson J, Athanacio J, Reynolds J, Laugero K, Guss S, Vu C, Roth J, and Parkes D (2007) Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight. Am J Physiol Regul Integr Comp Physiol 293:R1855–R1863.
161. Mack CM, Smith PA, Athanacio JR, Xu K, Wilson JK, Reynolds JM, Jodka CM, Lu MGW, and Parkes DG (2011) Glucoregulatory effects and prolonged duration of action of davalintide: a novel amylinomimetic peptide. Diabetes Obes Metab 13: 1105–1113.
162. Mack CM, Soares CJ, Wilson JK, Athanacio JR, Turek VF, Trevaskis JL, Roth JD, Smith PA, Gedulin B, and Jodka CM, et al. (2010) Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight. Int J Obes (Lond) 34:385–395.
163. Mather KJ, Paradisi G, Leaming R, Hook G, Steinberg HO, Fineberg N, Hanley R, and Baron AD (2002) Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity. Diabetes Metab Res Rev 18:118–126.
164. McGill M, Molyneaux L, Twigg SM, and Yue DK (2008) The metabolic syndrome in type 1 diabetes: does it exist and does it matter? J Diabetes Complications 22:18–23.
165. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, and Foord SM (1998) RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393:333–339.
166. Mehta NM, Sturmer A, and Stern W, and Gilligan JP (2013) inventors, Unigene Laboratories, assignee. Treatment for obesity. US Patent 8378067. 2013 Feb 19.
167. Mietlicki-Baase EG, Olivos DR, Jeffrey BA, and Hayes MR (2015) Cooperative interaction between leptin and amylin signaling in the ventral tegmental area for the control of food intake. Am J Physiol Endocrinol Metab DOI: 10.1152/ ajpendo.00087.2015 [published ahead of print].
168. Mietlicki-Baase EG, Rupprecht LE, Olivos DR, Zimmer DJ, Alter MD, Pierce RC, Schmidt HD, and Hayes MR (2013) Amylin receptor signaling in the ventral tegmental area is physiologically relevant for the control of food intake. Neuropsychopharmacology 38:1685–1697.
169. Mimee A, Smith PM, and Ferguson AV (2013) Circumventricular organs: targets for integration of circulating fluid and energy balance signals? Physiol Behav 121: 96–102.
170. Mollet A, Gilg S, Riediger T, and Lutz TA (2004) Infusion of the amylin antagonist AC 187 into the area postrema increases food intake in rats. Physiol Behav 81: 149–155.
171. Mollet A, Meier S, Grabler V, Gilg S, Scharrer E, and Lutz TA (2003a) Endogenous amylin contributes to the anorectic effects of cholecystokinin and bombesin. Peptides 24:91–98.
172. Mollet A, Meier S, Riediger T, and Lutz TA (2003b) Histamine H1 receptors in the ventromedial hypothalamus mediate the anorectic action of the pancreatic hormone amylin. Peptides 24:155–158.
173. Moon HS, Chamberland JP, Diakopoulos KN, Fiorenza CG, Ziemke F, Schneider B, and Mantzoros CS (2011) Leptin and amylin act in an additive manner to activate overlapping signaling pathways in peripheral tissues: in vitro and ex vivo studies in humans. Diabetes Care 34:132–138.
174. Morfis M, Tilakaratne N, Furness SG, Christopoulos G, Werry TD, Christopoulos A, and Sexton PM (2008) Receptor activity-modifying proteins differentially modulate the G protein-coupling efficiency of amylin receptors. Endocrinology 149: 5423–5431.
175. Morley JE, Flood JF, Horowitz M, Morley PM, and Walter MJ (1994) Modulation of food intake by peripherally administered amylin. Am J Physiol 267:R178–R184.
176. Morley JE, Morley PM, and Flood JF (1993) Anorectic effects of amylin in rats over the life span. Pharmacol Biochem Behav 44:577–580.
177. Morley JE, Suarez MD, Mattamal M, and Flood JF (1997) Amylin and food intake in mice: effects on motivation to eat and mechanism of action. Pharmacol Biochem Behav 56:123–129.
178. Moyses C, Kolterman O, and Mant T (1993) Pharmacokinetic and hyperglycaemic effects of the amylin analogue, AC137, in man. Diabetic Med 10:S25.
179. Muff R, Bühlmann N, Fischer JA, and Born W (1999) An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or -3. Endocrinology 140:2924–2927.
180. Müller TD, Sullivan LM, Habegger K, Yi C-X, Kabra D, Grant E, Ottaway N, Krishna R, Holland J, and Hembree J, et al. (2012) Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. J Pept Sci 18:383–393.
181. Nakamoto H, Soeda Y, Takami S, Minami M, and Satoh M (2000) Localization of calcitonin receptor mRNA in the mouse brain: coexistence with serotonin transporter mRNA. Brain Res Mol Brain Res 76:93–102.
182. Nakanome C, Akai H, Hongo M, Imai N, Toyota T, Goto Y, Okuguchi F, and Komatsu K (1983) Disturbances of the alimentary tract motility and hypermotilinemia in the patients with diabetes mellitus. Tohoku J Exp Med 139:205–215.
183. Nakazato M, Miyazato M, Asai J, Mitsukawa T, Kangawa K, Matsuo H, and Matsukura S (1990) Islet amyloid polypeptide, a novel pancreatic peptide, is a circulating hormone secreted under glucose stimulation. Biochem Biophys Res Commun 169:713–718.
184. Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, Hüfner M, and Schmiegel WH (2002) Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab 87:1239–1246.
185. Nicandro JPA, Ellero C, Pannacciulli N, Kesty NC, Deng W, Weyer C, and Chen HC (2008) AC2307, an amylin mimetic, reduced 24-h food intake in obese subjects (Abstract). Diabetes 57 (Suppl 1):A433.
186. Nyholm B, Møller N, Gravholt CH, Orskov L, Mengel A, Bryan G, Moyses C, Alberti KG, and Schmitz O (1996) Acute effects of the human amylin analog AC137 on basal and insulin-stimulated euglycemic and hypoglycemic fuel metabolism in patients with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 81:1083–1089.
187. Nyholm B, Orskov L, Hove KY, Gravholt CH, Møller N, Alberti KG, Moyses C, Kolterman O, and Schmitz O (1999) The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus. Metabolism 48:935–941.
188. Ogawa A, Harris V, McCorkle SK, Unger RH, and Luskey KL (1990) Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment. J Clin Invest 85:973–976.
189. Olgiati VR, Guidobono F, Netti C, and Pecile A (1983) Localization of calcitonin binding sites in rat central nervous system: evidence of its neuroactivity. Brain Res 265:209–215.
190. Oliver KR, Kane SA, Salvatore CA, Mallee JJ, Kinsey AM, Koblan KS, Keyvan- Fouladi N, Heavens RP, Wainwright A, and Jacobson M, et al. (2001) Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat. Eur J Neurosci 14:618–628.
191. Olsson M, Herrington MK, Reidelberger RD, Permert J, Gebre-Medhin S, and Arnelo U (2012) Food intake and meal pattern in IAPP knockout mice with and without infusion of exogenous IAPP. Scand J Gastroenterol 47:191–196.
192. Osaka T, Tsukamoto A, Koyama Y, and Inoue S (2008) Central and peripheral administration of amylin induces energy expenditure in anesthetized rats. Peptides 29:1028–1035.
193. Osto M, Wielinga PY, Alder B, Walser N, and Lutz TA (2007) Modulation of the satiating effect of amylin by central ghrelin, leptin and insulin. Physiol Behav 91: 566–572.
194. Perry KJ, Quiza M, Myers DE, Morfis M, Christopoulos G, and Sexton PM (1997) Characterization of amylin and calcitonin receptor binding in the mouse alphathyroid- stimulating hormone thyrotroph cell line. Endocrinology 138:3486–3496.
195. Pieber TR, Roitelman J, Lee Y, Luskey KL, and Stein DT (1994) Direct plasma radioimmunoassay for rat amylin-(1-37): concentrations with acquired and genetic obesity. Am J Physiol 267:E156–E164.
196. Plourde V, St-Pierre S, Fournier A, and Taché Y (1993) CGRP 8-37[correction of 8-27] blocks the inhibition of gastric emptying induced by intravenous injection of alpha- CGRP in rats. Life Sci 52:857–862.
197. Potes CS, Boyle CN, Wookey PJ, Riediger T, and Lutz TA (2012) Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin’s eating inhibitory effect. Am J Physiol Regul Integr Comp Physiol 302:R340–R351.
198. Potes CS and Lutz TA (2010) Brainstem mechanisms of amylin-induced anorexia. Physiol Behav 100:511–518.
199. Potes CS, Lutz TA, and Riediger T (2010a) Identification of central projections from amylin-activated neurons to the lateral hypothalamus. Brain Res 1334:31–44.
200. Potes CS, Riediger T, and Lutz TA (2010b) Amylin induces ERK 1/2 phosphorylation in structures of the AP/NTS-LPB-Ce-BSTL axis. Appetite 54:670.
201. Potes CS, Turek VF, Cole RL, Vu C, Roland BL, Roth JD, Riediger T, and Lutz TA (2010c) Noradrenergic neurons of the area postrema mediate amylin’s hypophagic action. Am J Physiol Regul Integr Comp Physiol 299:R623–R631.
202. Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, and Foord SM (2002) International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev 54:233–246.
203. Qi D, Cai K, Wang O, Li Z, Chen J, Deng B, Qian L, and Le Y (2010) Fatty acids induce amylin expression and secretion by pancreatic b-cells. Am J Physiol Endocrinol Metab 298:E99–E107.
204. Qi T, Christopoulos G, Bailey RJ, Christopoulos A, Sexton PM, and Hay DL (2008) Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. Mol Pharmacol 74:1059–1071.
205. Qi T, Dong M, Watkins HA, Wootten D, Miller LJ, and Hay DL (2013) Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant D(1-47)hCT((a)) function. Br J Pharmacol 168:644–657.
206. Ravussin E, Smith SR, Mitchell JA, Shringarpure R, Shan K, Maier H, Koda JE, and Weyer C (2009) Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring) 17:1736–1743.
207. Reidelberger R, Haver A, Chelikani PK, Apenteng B, Perriotte-Olson C, Anders K, Steenson S, and Blevins JE (2012) Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats. Am J Physiol Endocrinol Metab 302:E1576–E1585.
208. Reidelberger RD, Arnelo U, Granqvist L, and Permert J (2001) Comparative effects of amylin and cholecystokinin on food intake and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 280:R605–R611.
209. Reidelberger RD, Kelsey L, and Heimann D (2002) Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 282:R1395–R1404.
210. Riddle M, Pencek R, Charenkavanich S, Lutz K, Wilhelm K, and Porter L (2009) Randomized comparison of pramlintide or mealtime insulin added to basal insulin treatment for patients with type 2 diabetes. Diabetes Care 32:1577–1582.
211. Riediger T, Schmid HA, Lutz T, and Simon E (2001) Amylin potently activates AP neurons possibly via formation of the excitatory second messenger cGMP. Am J Physiol Regul Integr Comp Physiol 281:R1833–R1843.
212. Riediger T, Schmid HA, Lutz TA, and Simon E (2002) Amylin and glucose co-activate area postrema neurons of the rat. Neurosci Lett 328:121–124.
213. Riediger T, Schmid HA, Young AA, and Simon E (1999) Pharmacological characterisation of amylin-related peptides activating subfornical organ neurones. Brain Res 837:161–168.
214. Riediger T, Zuend D, Becskei C, and Lutz TA (2004) The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis. Am J Physiol Regul Integr Comp Physiol 286:R114–R122.
215. Riedy CA, Chavez M, Figlewicz DP, and Woods SC (1995) Central insulin enhances sensitivity to cholecystokinin. Physiol Behav 58:755–760.
216. Roth CL, Bongiovanni KD, Gohlke B, and Woelfle J (2010) Changes in dynamic insulin and gastrointestinal hormone secretion in obese children. J Pediatr Endocrinol Metab 23:1299–1309.
217. Roth JD, Coffey T, Jodka CM, Maier H, Athanacio JR, Mack CM, Weyer C, and Parkes DG (2007b) Combination therapy with amylin and peptide YY[3-36] in obese rodents: anorexigenic synergy and weight loss additivity. Endocrinology 148: 6054–6061.
218. Roth JD, D’Souza L, Griffin PS, Athanacio J, Trevaskis JL, Nazarbaghi R, Jodka C, Athanacio J, Hoyt J, and Forood B, et al. (2012) Interactions of amylinergic and melanocortinergic systems in the control of food intake and body weight in rodents. Diabetes Obes Metab 14:608–615.
219. Roth JD, Hughes H, Coffey T, Maier H, Trevaskis JL, and Anderson CM (2007a) Effects of prior or concurrent food restriction on amylin-induced changes in body weight and body composition in high-fat-fed female rats. Am J Physiol Endocrinol Metab 293:E1112–E1117.
220. Roth JD, Hughes H, Kendall E, Baron AD, and Anderson CM (2006) Antiobesity effects of the beta-cell hormone amylin in diet-induced obese rats: effects on food intake, body weight, composition, energy expenditure, and gene expression. Endocrinology 147:5855–5864.
221. Roth JD, Maier H, Chen S, and Roland BL (2009) Implications of amylin receptor agonism: integrated neurohormonal mechanisms and therapeutic applications. Arch Neurol 66:306–310.
222. Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, Anderson CM, Parkes DG, and Baron AD (2008a) Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 105:7257–7262.
223. Roth JD, Soares CJ, Ghosh SS, and Parkes DG (2008b) Amylin-based pharmacotherapy – past, present & future. Immunol Endocr Metab Agents Med Chem 8: 317–324.
224. Roth JD, Trevaskis JL, Wilson J, Lei C, Athanacio J, Mack C, Kesty NC, Coffey T, Weyer C, and Parkes DG (2008c) Antiobesity effects of the beta-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats. Int J Obes (Lond) 32:1201–1210.
225. Rowland NE, Crews EC, and Gentry RM (1997) Comparison of Fos induced in rat brain by GLP-1 and amylin. Regul Pept 71:171–174.
226. Rushing PA, Hagan MM, Seeley RJ, Lutz TA, D’Alessio DA, Air EL, and Woods SC (2001) Inhibition of central amylin signaling increases food intake and body adiposity in rats. Endocrinology 142:5035.
227. Rushing PA, Hagan MM, Seeley RJ, Lutz TA, and Woods SC (2000) Amylin: a novel action in the brain to reduce body weight. Endocrinology 141:850–853.
228. Sabharwal R, Zhang Z, Lu Y, Abboud FM, Russo AF, and Chapleau MW (2010) Receptor activity-modifying protein 1 increases baroreflex sensitivity and attenuates Angiotensin-induced hypertension. Hypertension 55:627–635.
229. Saetrum Opgaard O, de Vries R, Tom B, Edvinsson L, and Saxena PR (1999) Positive inotropy of calcitonin gene-related peptide and amylin on porcine isolated myocardium. Eur J Pharmacol 385:147–154.
230. Samsom M, Szarka LA, Camilleri M, Vella A, Zinsmeister AR, and Rizza RA (2000) Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibition. Am J Physiol Gastrointest Liver Physiol 278:G946–G951.
231. Schorr AB and Ofan R (2012) Simultaneous use of two external subcutaneous pumps delivering insulin and SYMLIN: use of a double-pump system. J Diabetes Sci Tech 6:1507–1508.
232. Sexton PM, Findlay DM, and Martin TJ (1999) Calcitonin. Curr Med Chem 6: 1067–1093.
233. Sexton PM, McKenzie JS, and Mendelsohn FA (1988) Evidence for a new subclass of calcitonin/ calcitonin gene-related peptide binding site in rat brain. Neurochem Int 12:323–335.
234. Sexton PM, Paxinos G, Huang XF, and Mendelsohn FA (1994a) In vitro autoradiographic localization of calcitonin binding sites in human medulla oblongata. J Comp Neurol 341:449–463.
235. Sexton PM, Paxinos G, Kenney MA, Wookey PJ, and Beaumont K (1994b) In vitro autoradiographic localization of amylin binding sites in rat brain. Neuroscience 62: 553–567.
236. Sibilia V, Pagani F, Lattuada N, Rapetti D, Guidobono F, and Netti C (2000) Amylin compared with calcitonin: competitive binding studies in rat brain and antinociceptive activity. Brain Res 854:79–84.
237. Silvestre RA, Rodríguez-Gallardo J, Jodka C, Parkes DG, Pittner RA, Young AA, and Marco J (2001) Selective amylin inhibition of the glucagon response to arginine is extrinsic to the pancreas. Am J Physiol Endocrinol Metab 280:E443–E449.
238. Singh-Franco D, Perez A, and Harrington C (2011) The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis. Diabetes Obes Metab 13:169–180.
239. Skofitsch G, Wimalawansa SJ, Jacobowitz DM, and Gubisch W (1995) Comparative immunohistochemical distribution of amylin-like and calcitonin gene related peptide like immunoreactivity in the rat central nervous system. Can J Physiol Pharmacol 73:945–956.
240. Smeltzer M, Scott K, Melhorn S, Krause E, and Sakai R (2012) Amylin blunts hyperphagia and reduces weight and fat gain during recovery in socially stressed rats. Am J Physiol Regul Integr Comp Physiol 303:R676–R682.
241. Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, and Weyer C (2008) Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care 31:1816–1823.
242. Smith SR, Blundell JE, Burns C, Ellero C, Schroeder BE, Kesty NC, Chen KS, Halseth AE, Lush CW, and Weyer C (2007) Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6- wk translational research study. Am J Physiol Endocrinol Metab 293:E620–E627.
243. Stachniak TJE and Krukoff TL (2003) Receptor activity modifying protein 2 distribution in the rat central nervous system and regulation by changes in blood pressure. J Neuroendocrinol 15:840–850.
244. Surina-Baumgartner DM, Langhans W, and Geary N (1995) Hepatic portal insulin antibody infusion increases, but insulin does not alter, spontaneous meal size in rats. Am J Physiol 269:R978–R982.
245. Szabó ÉR, Cservenák M, and Dobolyi A (2012) Amylin is a novel neuropeptide with potential maternal functions in the rat. FASEB J 26:272–281.
246. Tam CW, Husmann K, Clark NC, Clark JE, Lazar Z, Ittner LM, Götz J, Douglas G, Grant AD, and Sugden D, et al. (2006) Enhanced vascular responses to adrenomedullin in mice overexpressing receptor-activity-modifying protein 2. Circ Res 98: 262–270.
247. Tashjian AH Jr, Wright DR, Ivey JL, and Pont A (1978) Calcitonin binding sites in bone: relationships to biological response and “escape.” Recent Prog Horm Res 34: 285–334.
248. Tilakaratne N, Christopoulos G, Zumpe ET, Foord SM, and Sexton PM (2000) Amylin receptor phenotypes derived from human calcitonin receptor/RAMP coexpression exhibit pharmacological differences dependent on receptor isoform and host cell environment. J Pharmacol Exp Ther 294:61–72.
249. Tingstedt JE, Edlund H, Madsen OD, and Larsson LI (1999) Gastric amylin expression. Cellular identity and lack of requirement for the homeobox protein PDX- 1. A study in normal and PDX-1-deficient animals with a cautionary note on antiserum evaluation. J Histochem Cytochem 47:973–980.
250. Tomabechi Y, Krippner G, Rendle PM, Squire MA, and Fairbanks AJ (2013) Glycosylation of pramlintide: synthetic glycopeptides that display in vitro and in vivo activities as amylin receptor agonists. Chemistry 19:15084–15088.
251. Trevaskis JL, Coffey T, Cole R, Lei C, Wittmer C, Walsh B, Weyer C, Koda J, Baron AD, and Parkes DG, et al. (2008) Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology 149:5679–5687.
252. Trevaskis JL, Lei C, Koda JE, Weyer C, Parkes DG, and Roth JD (2010a) Interaction of leptin and amylin in the long-term maintenance of weight loss in diet-induced obese rats. Obesity (Silver Spring) 18:21–26.
253. Trevaskis JL, Parkes DG, and Roth JD (2010b) Insights into amylin-leptin synergy. Trends Endocrinol Metab 21:473–479.
254. Trevaskis JL, Turek VF, Wittmer C, Griffin PS, Wilson JK, Reynolds JM, Zhao Y, Mack CM, Parkes DG, and Roth JD (2010c) Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced obese rats. Endocrinology 151: 5657–5668.
255. Turek VF, Trevaskis JL, Levin BE, Dunn-Meynell AA, Irani B, Gu G, Wittmer C, Griffin PS, Vu C, and Parkes DG, et al. (2010) Mechanisms of amylin/leptin synergy in rodent models. Endocrinology 151:143–152.
256. Turner AG, Tjahyono F, Chiu WSM, Skinner J, Sawyer R, Moore AJ, Morris HA, Findlay DM, Zajac JD, and Davey RA (2011) The role of the calcitonin receptor in protecting against induced hypercalcemia is mediated via its actions in osteoclasts to inhibit bone resorption. Bone 48:354–361.
257. Udawela M, Christopoulos G, Morfis M, Christopoulos A, Ye S, Tilakaratne N, and Sexton PM (2006a) A critical role for the short intracellular C terminus in receptor activity-modifying protein function. Mol Pharmacol 70:1750–1760.
258. Udawela M, Christopoulos G, Tilakaratne N, Christopoulos A, Albiston A, and Sexton PM (2006b) Distinct receptor activity-modifying protein domains differentially modulate interaction with calcitonin receptors. Mol Pharmacol 69: 1984–1989.
259. Udawela M, Christopoulos G, Morfis M, Tilakaratne N, Christopoulos A, and Sexton PM (2008) The effects of C-terminal truncation of receptor activity modifying proteins on the induction of amylin receptor phenotype from human CTb receptors. Regul Pept 145:65–71.
260. Ueda T, Ugawa S, Saishin Y, and Shimada S (2001) Expression of receptor-activity modifying protein (RAMP) mRNAs in the mouse brain. Brain Res Mol Brain Res 93:36–45.
261. Vine W, Smith P, LaChappell R, Blase E, Lumpkin R, and Young A (1998a) Nephrectomy decreases amylin and pramlintide clearance in rats. Horm Metab Res 30:514–517.
262. Vine W, Smith P, LaChappell R, Blase E, and Young A (1998b) Effects of rat amylin on renal function in the rat. Horm Metab Res 30:518–522.
263. Visa M, Alcarraz-Vizan G, Montane J, Cadavez L, Castano C, Villanueva-Penacarrillo ML, Servitja JM, and Novials A (2015) Islet amyloid polypeptide exerts a novel autocrine action in b-cell signaling and proliferation. FASEB J DOI: 10.1096/fj.15-270553 [published ahead of print]
264. Walker CS, Eftekhari S, Bower RL, Wilderman A, Insel PA, Edvinsson L, Waldvogel HJ, Jamaluddin MA, Russo AF, and Hay DL (2015) A second trigeminal CGRP receptor: function and expression of the AMY1 receptor. Ann Clin Transl Neurol DOI: 10.1002/acn3.197 [published ahead of print]
265. Walker CS, Li X, Whiting L, Glyn-Jones S, Zhang S, Hickey AJ, Sewell MA, Ruggiero K, Phillips ARJ, and Kraegen EW, et al. (2010) Mice lacking the neuropeptide a-calcitonin gene-related peptide are protected against diet-induced obesity. Endocrinology 151:4257–4269.
266. Wauman J and Tavernier J (2011) Leptin receptor signaling: pathways to leptin resistance. Front Biosci (Landmark Ed) 16:2771–2793.
267. Weinzimer SA, Sherr JL, Cengiz E, Kim G, Ruiz JL, Carria L, Voskanyan G, Roy A, and Tamborlane WV (2012) Effect of pramlintide on prandial glycemic excursions during closed-loop control in adolescents and young adults with type 1 diabetes. Diabetes Care 35:1994–1999.
268. West DB, Fey D, and Woods SC (1984) Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 246:R776–R787.
269. Westermark P, Andersson A, and Westermark GT (2011) Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev 91:795–826.
270. Westermark P, Wernstedt C, O’Brien TD, Hayden DW, and Johnson KH (1987a) Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone. Am J Pathol 127:414–417.
271. Westermark P, Wernstedt C, Wilander E, Hayden DW, O’Brien TD, and Johnson KH (1987b) Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci USA 84:3881–3885.
272. Westermark P, Wernstedt C, Wilander E, and Sletten K (1986) A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas. Biochem Biophys Res Commun 140:827–831.
273. Weyer C, Fineman MS, Strobel S, Shen L, Data J, Kolterman OG, and Sylvestri MF (2005) Properties of pramlintide and insulin upon mixing. Am J Health Syst Pharm 62:816–822.
274. Weyer C, Maggs DG, Young AA, and Kolterman OG (2001) Amylin replacement with pramlintide as an adjunct to insulin therapy in type 1 and type 2 diabetes mellitus: a physiological approach toward improved metabolic control. Curr Pharm Des 7: 1353–1373.
275. Wickbom J, Herrington MK, Permert J, Jansson A, and Arnelo U (2008) Gastric emptying in response to IAPP and CCK in rats with subdiaphragmatic afferent vagotomy. Regul Pept 148:21–25.
276. Wielinga PY, Alder B, and Lutz TA (2007) The acute effect of amylin and salmon calcitonin on energy expenditure. Physiol Behav 91:212–217.
277. Wielinga PY, Löwenstein C, Alder B, and Lutz TA (2008) Effect of peripheral and central amylin on energy expenditure and body temperature. Appetite 91:409.
278. Wielinga PY, Löwenstein C, Muff S, Munz M, Woods SC, and Lutz TA (2010) Central amylin acts as an adiposity signal to control body weight and energy expenditure. Physiol Behav 101:45–52.
279. Wong WP, Scott DW, Chuang CL, Zhang S, Liu H, Ferreira A, Saafi EL, Choong YS, and Cooper GJ (2008) Spontaneous diabetes in hemizygous human amylin transgenic mice that developed neither islet amyloid nor peripheral insulin resistance. Diabetes 57:2737–2744.
280. Woods SC (2005) Signals that influence food intake and body weight. Physiol Behav 86:709–716.
281. Wookey PJ, Cao Z, van Geenen RC, Voskuil M, Darby IA, Komers R, and Cooper ME (1997) Increased density of renal amylin binding sites in experimental hypertension. Hypertension 30:455–460.
282. Wookey PJ and Cooper ME (1998) Amylin: physiological roles in the kidney and a hypothesis for its role in hypertension. Clin Exp Pharmacol Physiol 25:653–660.
283. Wookey PJ, Tikellis C, Nobes M, Casley D, Cooper ME, and Darby IA (1998) Amylin as a growth factor during fetal and postnatal development of the rat kidney. Kidney Int 53:25–30.
284. Yang Y and Song W (2013) Molecular links between Alzheimer’s disease and diabetes mellitus. Neuroscience 250:140–150.
285. Young A (1997) Role of amylin in nutrient intake - animal studies. Diabet Med 14 (Suppl 2):S14–S18.
286. Young A (2005a) Cardiovascular effects. Adv Pharmacol 52:239–250.
287. Young A (2005b) Inhibition of gastric emptying. Adv Pharmacol 52:99–121.
288. Young A (2005c) Inhibition of glucagon secretion. Adv Pharmacol 52:151–171.
289. Young A (2005d) Tissue expression and secretion of amylin. Adv Pharmacol 52: 19–45.
290. Young A and Denaro M (1998) Roles of amylin in diabetes and in regulation of nutrient load. Nutrition 14:524–527.
291. Young A, Kolterman O, and Hall J (1999) Amylin innocent in essential hypertension? Diabetologia 42:1029.
292. Young AA (2012) Brainstem sensing of meal-related signals in energy homeostasis. Neuropharmacology 63:31–45.
293. Young AA, Gedulin B, Vine W, Percy A, and Rink TJ (1995) Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin. Diabetologia 38:642–648.
294. Young AA, Gedulin BR, and Rink TJ (1996a) Dose-responses for the slowing of gastric emptying in a rodent model by glucagon-like peptide (7-36) NH2, amylin, cholecystokinin, and other possible regulators of nutrient uptake. Metabolism 45: 1–3.
295. Young AA, Vine W, Gedulin BR, Pittner R, Janes S, Gaeta LSL, Percy A, Moore CX, Koda JE, and Rink TJ, et al. (1996b) Preclinical pharmacology of pramlintide in the rat: Comparisons with human and rat amylin. Drug Dev Res 37:231–248.
296. Young AA, Wang MW, and Cooper GJ (1991) Amylin injection causes elevated plasma lactate and glucose in the rat. FEBS Lett 291:101–104.
297. Younk LM, Mikeladze M, and Davis SN (2011) Pramlintide and the treatment of diabetes: a review of the data since its introduction. Expert Opin Pharmacother 12: 1439–1451.
298. Zaki M, Koduru S, McCuen R, Vuyyuru L, and Schubert ML (2002) Amylin, released from the gastric fundus, stimulates somatostatin and thus inhibits histamine and acid secretion in mice. Gastroenterology 123:247–255.
299. Zhang Y and Scarpace PJ (2006) The role of leptin in leptin resistance and obesity. Physiol Behav 88:249–256.
300. Zhang Z, Liu X, Morgan DA, Kuburas A, Thedens DR, Russo AF, and Rahmouni K (2011) Neuronal receptor activity-modifying protein 1 promotes energy expenditure in mice. Diabetes 60:1063–1071.
301. Zhang Z, Winborn CS, Marquez de Prado B, and Russo AF (2007) Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion. J Neurosci 27:2693–2703.
302. Zhou Y and Rui L (2013) Leptin signaling and leptin resistance. Fr Medecine 7:207–222.
303. Zhu H, Wang X, Wallack M, Li H, Carreras I, Dedeoglu A, Hur JY, Zheng H, Fine R, and Mwamburi M, et al. (2015) Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer’s disease. Mol Psychiatry 20:252–262.
304. Züger D, Forster K, Lutz TA, and Riediger T (2013) Amylin and GLP-1 target different populations of area postrema neurons that are both modulated by nutrient stimuli. Physiol Behav 112–113:61–69.