Gut-brain axis: Regulation of glucose metabolism

Journal of Neuroendocrinology

Volumn 18, Issue 12, 2006, Pages 883-894

  Heijboer, A C ^a   Pijl, H ^a   van den Hoek, A M ^a,b   Havekes, L M ^a,b   Romijn, J A ^a   Corssmit, E P M ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b TNO   (Netherlands)

Author keywords

Gastric delay; Glucose metabolism; Gut motility; Guthormones; Hypothalamus; Insulin secretion; Insulin sensitivity; Obesity; Satiety

Indexed keywords

CHOLECYSTOKININ; GASTRIC INHIBITORY POLYPEPTIDE; GASTROINTESTINAL HORMONE; GHRELIN; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; INSULIN; OXYNTOMODULIN; PEPTIDE YY;

BODY WEIGHT; BRAIN; ENERGY METABOLISM; FOOD INTAKE; GASTROINTESTINAL MOTILITY; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; HORMONE ACTION; HUMAN; HYPOTHALAMUS; INSULIN RELEASE; INSULIN SENSITIVITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SATIETY;

APPETITE REGULATION; ENERGY METABOLISM; ENTERIC NERVOUS SYSTEM; GASTROINTESTINAL HORMONES; GASTROINTESTINAL TRACT; GLUCOSE; HUMANS; HYPOTHALAMUS; NEUROSECRETORY SYSTEMS; PEPTIDE HORMONES;

EID: 33750494957     PISSN: 09538194     EISSN: 13652826     Source Type: Journal    
DOI: 10.1111/j.1365-2826.2006.01492.x     Document Type: Review

References (174)

1. World Health Ogranization. Data available online. http://www.who.int, 2006.
2. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors. JAMA 2001; 289: 76-79.
3. Andreyeva T, Sturm R, Ringel JS. Moderate and severe obesity have large differences in health care costs. Obes Res 2004; 12: 1936-1943.
4. Renshaw D, Batterham RL. Peptide YY: A potential therapy for obesity. Curr Drug Targets 2005; 6: 171-179.
5. Schwartz MW, Porte D Jr. Diabetes, obesity, and the brain. Science 2005; 307: 375-379.
6. Stellar E. The physiology of motivation. Psychol Rev 1954; 61: 5-22.
7. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000; 404: 661-671.
8. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999; 20: 68-100.
9. Cone RD, Cowley MA, Butler AA, Fan W, Marks DL, Low MJ. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord 2001; 25 (Suppl. 5): S63-S67.
10. Cowley MA, Cone RD, Enriori P, Louiselle I, Williams SM, Evans AE. Electrophysiological actions of peripheral hormones on melanocortin neurons. Ann NY Acad Sci 2003; 994: 175-186.
11. Hillebrand JJ, de Wied D, Adan RA. Neuropeptides, food intake and body weight regulation: A hypothalamic focus. Peptides 2002; 23: 2283-2306.
12. Lee HM, Wang G, Englander EW, Kojima M, Greeley GH Jr. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 2002; 143: 185-190.
13. Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely AJ, Deghenghi R, Ghigo E. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 2001; 86: 5083-5086.
14. Mizuno TM, Makimura H, Silverstein J, Roberts JL, Lopingco T, Mobbs CV. Fasting regulates hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocortin in diabetic mice independent of changes in leptin or insulin. Endocrinology 1999; 140: 4551-4557.
15. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 1999; 5: 1066-1070.
16. Fan W, Dinulescu DM, Butler AA, Zhou J, Marks DL, Cone RD. The central melanocortin system can directly regulate serum insulin levels. Endocrinology 2000; 141: 3072-3079.
17. Krude H, Gruters A. Implications of proopiomelanocortin (POMC) mutations in humans: The POMC deficiency syndrome. Trends Endocrinol Metab 2000; 11: 15-22.
18. Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 1998; 20: 111-112.
19. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348: 1085-1095.
20. Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 1998; 20: 113-114.
21. del Giudice EM, Santoro N, Cirillo G, D'Urso L, Di Toro R, Perrone L. Mutational screening of the CART gene in obese children: Identifying a mutation (Leu34Phe) associated with reduced resting energy expenditure and cosegregating with obesity phenotype in a large family. Diabetes 2001; 50: 2157-2160.
22. Wynne K, Stanley S, Bloom S. The gut and regulation of body weight. J Clin Endocrinol Metab 2004; 89: 2576-2582.
23. Korner J, Leibel RL. To eat or not to eat - how the gut talks to the brain. N Engl J Med 2003; 349: 926-928.
24. Abbott CR, Small CJ, Kennedy AR, Neary NM, Sajedi A, Ghatei MA, Bloom SR. Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3-36) on food intake. Brain Res 2005; 1043: 139-144.
25. Abbott CR, Monteiro M, Small CJ, Sajedi A, Smith KL, Parkinson JR, Ghatei MA, Bloom SR. The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res 2005; 1044: 127-131.
26. Koda S, Date Y, Murakami N, Shimbara T, Hanada T, Toshinai K, Niijima A, Furuya M, Inomata N, Osuye K, Nakazato M. The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 2005; 146: 2369-2375.
27. Small CJ, Bloom SR. Gut hormones and the control of appetite. Trends Endocrinol Metab 2004; 15: 259-263.
28. Neary NM, Goldstone AP, Bloom SR. Appetite regulation: From the gut to the hypothalamus. Clin Endocrinol (Oxf) 2004; 60: 153-160.
29. Strader AD, Woods SC. Gastrointestinal hormones and food intake. Gastroenterology 2005; 128: 175-191.
30. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001; 50: 1714-1719.
31. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656-660.
32. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407: 908-913.
33. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000; 141: 4325-4328.
34. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992.
35. Shrestha YB, Wickwire K, Giraudo SQ. Action of MT-II on ghrelin-induced feeding in the paraventricular nucleus of the hypothalamus. Neuroreport 2004; 15: 1365-1367.
36. Lawrence CB, Snape AC, Baudoin FM, Luckman SM. Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 2002; 143: 155-162.
37. Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 2001; 50: 227-232.
38. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, Mckee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Van der Ploeg LH. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996; 273: 974-977.
39. Muccioli G, Ghe C, Ghigo MC, Papotti M, Arvat E, Boghen MF, Nilsson MH, Deghenghi R, Ong H, Ghigo E. Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland. J Endocrinol 1998; 157: 99-106.
40. Guan XMYuH, Palyha OC, Mckee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD. Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 1997; 48: 23-29.
41. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 2002; 123: 1120-1128.
42. Neary NM, Druce MR, Small CJ, Bloom SR. Acylated ghrelin stimulates food intake in the fed and fasted states but desacylated ghrelin has no effect. Gut 2006; 55: 135.
43. Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 1973; 84: 488-495.
44. Polak JM, Bloom SR, Rayford PL, Pearse AG, Buchan AM, Thompson JC. Identification of cholecystokinin-secreting cells. Lancet 1975; 2: 1016-1018.
45. Dufresne M, Seva C, Fourmy D. Cholecystokinin and gastrin receptors. Physiol Rev 2006; 86: 805-847.
46. Lorenz DN, Goldman SA. Vagal mediation of the cholecystokinin satiety effect in rats. Physiol Behav 1982; 29: 599-604.
47. Moran TH, Baldessarini AR, Salorio CF, Lowery T, Schwartz GJ. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am J Physiol 1997; 272: R1245-R1251.
48. Edwards GL, Ladenheim EE, Ritter RC. Dorsomedial hindbrain participation in cholecystokinin-induced satiety. Am J Physiol 1986; 251: R971-R977.
49. Fan W, Ellacott KL, Halatchev IG, Takahashi KYuP, Cone RD. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci 2004; 7: 335-336.
50. Tschop M, Castaneda TR, Joost HG, Thone-Reineke C, Ortmann S, Klaus S, Hagan MM, Chandler PC, Oswald KD, Benoit SC, Seeley RJ, Kinzig KP, Moran TH, Beck-sickinger AG, Koglin N, Rodgers RJ, Blundell JE, Ishii Y, Beattie AH, Holch P, Allison DB, Raun K, Madsen K, Wulff BS, Stidsen CE, Birringer M, Kreuzer OJ, Schindler M, Arndt K, Rudolf K, Mark M, Deng XY, Whitcomb DC, Halem H, Taylor J, Dong J, Datta R, Culler M, Craney S, Flora D, Smiley D, Heiman ML. Physiology: Does gut hormone PYY3-36 decrease food intake in rodents? Nature 2004; 430: 1.
51. Furnsinn C, Ebner K, Waldhausl W. Failure of GLP-1(7-36) amide to affect glycogenesis in rat skeletal muscle. Diabetologia 1995; 38: 864-867.
52. Vella A, Shah P, Basu R, Basu A, Holst JJ, Rizza RA. Effect of glucagon-like peptide 1 (7-36): Amide on glucose effectiveness and insulin action in people with type 2 diabetes. Diabetes 2000; 49: 611-617.
53. Orskov L, Holst JJ, Moller J, Orskov C, Moller N, Alberti KG, Schmitz O. GLP-1 does not not acutely affect insulin sensitivity in healthy man. Diabetologia 1996; 39: 1227-1232.
54. Larsson H, Holst JJ, Ahren B. Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. Acta Physiol Scand 1997; 160: 413-422.
55. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002; 418: 650-654.
56. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003; 349: 941-948.
57. Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann NY Acad Sci 2003; 994: 162-168.
58. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP, Smith DM, Ghatei MA, Herbert J, Bloom SR. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996; 379: 69-72.
59. Verdich C, Flint A, Gutzwiller JP, Naslund E, Beglinger C, Hellstrom PM, Long SJ, Morgan LM, Holst JJ, Astrup A. A meta-analysis of the effect of glucagon-like peptide- 1 (7-36): Amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 2001; 86: 4382-4389.
60. Navarro M, Rodriquez DF, Alvarez E, Chowen JA, Zueco JA, Gomez R, Eng J, Blazquez E. Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: Evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake. J Neurochem 1996; 67: 1982-1991.
61. Shughrue PJ, Lane MV, Merchenthaler I. Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus. Endocrinology 1996; 137: 5159-5162.
62. Tang-Christensen M, Larsen PJ, Thulesen J, Romer J, Vrang N. The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat Med 2000; 6: 802-807.
63. Schmidt PT, Naslund E, Gryback P, Jacobsson H, Hartmann B, Holst JJ, Hellstrom PM. Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety. Regul Pept 2003; 116: 21-25.
64. Nagell CF, Wettergren A, Pedersen JF, Mortensen D, Holst JJ. Glucagon-like peptide-2 inhibits antral emptying in man, but is not as potent as glucagon-like peptide-1. Scand J Gastroenterol 2004; 39: 353-358.
65. Sorensen LB, Flint A, Raben A, Hartmann B, Holst JJ, Astrup A. No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. Int J Obes Relat Metab Disord 2003; 27: 450-456.
66. Le Quellec A, Kervran A, Blache P, Ciurana AJ, Bataille D. Oxyntomodulin-like immunoreactivity: Diurnal profile of a new potential enterogastrone. J Clin Endocrinol Metab 1992; 74: 1405-1409.
67. Ghatei MA, Uttenthal LO, Christofides ND, Bryant MG, Bloom SR. Molecular forms of human enteroglucagon in tissue and plasma: Plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract. J Clin Endocrinol Metab 1983; 57: 488-495.
68. Dakin CL, Small CJ, Batterham RL, Neary NM, Cohen MA, Patterson M, Ghatei MA, Bloom SR. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 2004; 145: 2687-2695.
69. Dakin CL, Small CJ, Park AJ, Seth A, Ghatei MA, Bloom SR. Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats. Am J Physiol Endocrinol Metab 2002; 283: E1173-E1177.
70. Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, Bloom SR. Oxyntomodulin inhibits food intake in the rat. Endocrinology 2001; 142: 4244-4250.
71. Mortensen K, Christensen LL, Holst JJ, Orskov C. GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul Pept 2003; 114: 189-196.
72. Woods SC, West DB, Stein LJ, Mckay LD, Lotter EC, Porte SG, Kenney NJ, Porte D Jr. Peptides and the control of meal size. Diabetologia 1981; 20 (Suppl.): 305-313.
73. Lorenz DN, Kreielsheimer G, Smith GP. Effect of cholecystokinin, gastrin, secretin and GIP on sham feeding in the rat. Physiol Behav 1979; 23: 1065-1072.
74. Cahill GF Jr, Herrera MG, Morgan AP, Soeldner JS, Steinke J, Levy PL, Reichard GA Jr, Kipnis DM. Hormone-fuel interrelationships during fasting. J Clin Invest 1966; 45: 1751-1769.
75. Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF Jr. Brain metabolism during fasting. J Clin Invest 1967; 46: 1589-1595.
76. Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr. Liver and kidney metabolism during prolonged starvation. J Clin Invest 1969; 48: 574-583.
77. Conti F. Claude Bernard: Primer of the second biomedical revolution. Nat Rev Mol Cell Biol 2001; 2: 703-708.
78. Bernard C. Chiens rendu diabetique. Comp Rend Soc Biol Paris 1850; 1: 60.
79. Frohman LA, Bernardis LL. Effect of hypothalamic stimulation on plasma glucose, insulin, and glucagon levels. Am J Physiol 1971; 221: 1596-1603.
80. Kreier F, Kalsbeek A, Ruiter M, Yilmaz A, Romijn JA, Sauerwein HP, Fliers E, Buijs RM. Central nervous determination of food storage - a daily switch from conservation to expenditure: Implications for the metabolic syndrome. Eur J Pharmacol 2003; 480: 51-65.
81. Woods SC, Lotter EC, Mckay LD, Porte D Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979; 282: 503-505.
82. Benoit SC, Air EL, Coolen LM, Strauss R, Jackman A, Clegg DJ, Seeley RJ, Woods SC. The catabolic action of insulin in the brain is mediated by melanocortins. J Neurosci 2002; 22: 9048-9052.
83. Schwartz MW, Sipols AJ, Marks JL, Sanacora G, White JD, Scheurink A, Kahn SE, Baskin DG, Woods SC, Figlewicz DP. Inhibition of hypothalamic neuropeptide Y gene expression by insulin. Endocrinology 1992; 130: 3608-3616.
84. Sipols AJ, Baskin DG, Schwartz MW. Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes 1995; 44: 147-151.
85. Okamoto H, Nakae J, Kitamura T, Park BC, Dragatsis I, Accili D. Transgenic rescue of insulin receptor-deficient mice. J Clin Invest 2004; 114: 214-223.
86. Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 2002; 8: 1376-1382.
87. Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci 2002; 5: 566-572.
88. Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR. Role of brain insulin receptor in control of body weight and reproduction. Science 2000; 289: 2122-2125.
89. Nordman S, Ding B, Ostenson CG, Karvestedt L, Brismar K, Efendic S, Gu HF. Leu7Pro polymorphism in the neuropeptide Y (NPY) gene is associated with impaired glucose tolerance and type 2 diabetes in Swedish men. Exp Clin Endocrinol Diabetes 2005; 113: 282-287.
90. Levine AS, Jewett DC, Cleary JP, Kotz CM, Billington CJ. Our journey with neuropeptide Y: Effects on ingestive behaviors and energy expenditure. Peptides 2004; 25: 505-510.
91. Marks JL, Waite K. Intracerebroventricular neuropeptide Y acutely influences glucose metabolism and insulin sensitivity in the rat. J Neuroendocrinol 1997; 9: 99-103.
92. van den Hoek AM, Voshol PJ, Karnekamp BN, Buijs RM, Romijn JA, Havekes LM, Pijl H. Intracerebroventricular neuropeptide Y infusion precludes inhibition of glucose and VLDL production by insulin. Diabetes 2004; 53: 2529-2534.
93. Obici S, Feng Z, Tan J, Liu L, Karkanias G, Rossetti L. Central melanocortin receptors regulate insulin action. J Clin Invest 2001; 108: 1079-1085.
94. Heijboer AC, van den Hoek AM, Pijl H, Voshol PJ, Havekes LM, Romijn JA, Corssmit EP. Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice. Diabetologia 2005; 48: 1621-1626.
95. Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H, Kojima M, Kangawa K. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 2000; 276: 905-908.
96. Edholm T, Levin F, Hellstrom PM, Schmidt PT. Ghrelin stimulates motility in the small intestine of rats through intrinsic cholinergic neurons. Regul Pept 2004; 121: 25-30.
97. Kitazawa T, De Smet B, Verbeke K, Depoortere I, Peeters TL. Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo and in vitro. Gut 2005; 54: 1078-1084.
98. Tack J, Depoortere I, Bisschops R, Delporte C, Coulie B, Meulemans A, Janssens J, Peeters T. Influence of ghrelin on interdigestive gastrointestinal motility in man Gut 2005; 22: 847-853.
99. Reimer MK, Pacini G, Ahren B. Dose-dependent inhibition by ghrelin of insulin secretion in the mouse. Endocrinology 2003; 144: 916-921.
100. Purnell JQ, Weigle DS, Breen P. Cummings DE. Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 2003; 88: 5747-5752.
101. Schofl C, Horn R, Schill T, Schlosser HW, Muller MJ, Brabant G. Circulating ghrelin levels in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 4607-4610.
102. Mclaughlin T, Abbasi F, Lamendola C, Frayo RS. Cummings DE. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 2004; 89: 1630-1635.
103. Ikezaki A, Hosoda H, Ito K, Iwama S, Miura N, Matsuoka H, Kondo C, Kojima M, Kangawa K, Sugihara S. Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes 2002; 51: 3408-3411.
104. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707-709.
105. Bunt JC, Salbe AD, Tschop MH, Delparigi A, Daychild P, Tataranni PA. Cross-sectional and prospective relationships of fasting plasma ghrelin concentrations with anthropometric measures in pima Indian children. J Clin Endocrinol Metab 2003; 88: 3756-3761.
106. Bacha F, Arslanian SA. Ghrelin suppression in overweight children: A manifestation of insulin resistance? J Clin Endocrinol Metab 2005; 90: 2725-2730.
107. Gimenez-Palop O, Gimenez-Perez G, Mauricio D, Berlanga E, Potau N, Vilardell C, Arroyo J, Gonzalez-Clemente JM, Caixas A. Circulating ghrelin in thyroid dysfunction is related to insulin resistance and not to hunger, food intake or anthropometric changes. Eur J Endocrinol 2005; 153: 73-79.
108. Pagotto U, Gambineri A, Vicennati V, Heiman ML, Tschop M, Pasquali R. Plasma ghrelin, obesity, and the polycystic ovary syndrome: Correlation with insulin resistance and androgen levels. J Clin Endocrinol Metab 2002; 87: 5625-5629.
109. Poykko SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 2003; 52: 2546-2553.
110. Heijboer AC, van den Hoek AM, Parlevliet ET, Havekes LM, Romijn JA, Pijl H, Corssmit EP. Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice. Diabetologia 2006; 49: 732-738.
111. Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ, Ghigo E, van der Lely AJ. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 2005; 90: 1055-1060.
112. Murata M, Okimura Y, Iida K, Matsumoto M, Sowa H, Kaji H, Kojima M, Kangawa K, Chihara K. Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J Biol Chem 2002; 277: 5667-5674.
113. Yoshimoto A, Mori K, Sugawara A, Mukoyama M, Yahata K, Suganami T, Takaya K, Hosoda H, Kojima M, Kangawa K, Nakao K. Plasma ghrelin and desacyl ghrelin concentrations in renal failure. J Am Soc Nephrol 2002; 13: 2748-2752.
114. Hotta M, Ohwada R, Katakami H, Shibasaki T, Hizuka N, Takano K. Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa. J Clin Endocrinol Metab 2004; 89: 5707-5712.
115. Currie PJ, Mirza A, Fuld R, Park D, Vasselli JR. Ghrelin is an orexigenic and metabolic signaling peptide in the arcuate and paraventricular nuclei Am J Physiol Regul Integr Comp Physiol 2005; 289: R353-R358.
116. Liddle RA, Rushakoff RJ, Morita ET, Beccaria L, Carter JD, Goldfine ID. Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans. J Clin Invest 1988; 81: 1675-1681.
117. Otsuki M, Sakamoto C, Yuu H, Maeda M, Morita S, Ohki A, Kobayashi N, Terashi K, Okano K, Baba S. Discrepancies between the doses of cholecystokinin or caerulein-stimulating exocrine and endocrine responses in perfused isolated rat pancreas. J Clin Invest 1979; 63: 478-484.
118. Szecowka J, Lins PE, Efendic S. Effects of cholecystokinin, gastric inhibitory polypeptide, and secretin on insulin and glucagon secretion in rats. Endocrinology 1982; 110: 1268-1272.
119. Hermansen K. Effects of cholecystokinin (CCK)-4, nonsulfated CCK-8, and sulfated CCK-8 on pancreatic somatostatin, insulin, and glucagon secretion in the dog: Studies in vitro. Endocrinology 1984; 114: 1770-1775.
120. Verspohl EJ, Ammon HP, Williams JA, Goldfine ID. Evidence that cholecystokinin interacts with specific receptors and regulates insulin release in isolated rat islets of Langerhans. Diabetes 1986; 35: 38-43.
121. Rushakoff RJ, Goldfine ID, Carter JD, Liddle RA. Physiological concentrations of cholecystokinin stimulate amino acid-induced insulin release in humans. J Clin Endocrinol Metab 1987; 65: 395-401.
122. Moran TH, Smedh U, Kinzig KP, Scott KA, Knipp S, Ladenheim EE. Peptide YY(3-36) inhibits gastric emptying and produces acute reductions in food intake in rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 2005; 288: R384-R388.
123. Bertrand G, Gross R, Roye M, Ahren B, Ribes G. Evidence for a direct inhibitory effect of PYY on insulin secretion in rats. Pancreas 1992; 7: 595-600.
124. Torekov SS, Larsen LH, Glumer C, Borch-Johnsen K, Jorgensen T, Holst JJ, Madsen OD, Hansen T, Pedersen O. Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes. Diabetes 2005; 54: 2261-2265.
125. van den Hoek AM, Heijboer AC, Corssmit EP, Voshol PJ, Romijn JA, Havekes LM, Pijl H. PYY3-36 reinforces insulin action on glucose disposal in mice fed a high-fat diet. Diabetes 2004; 53: 1949-1952.
126. Adams SH, Lei C, Jodka CM, Nikoulina SE, Hoyt JA, Gedulin B, Mack CM, Kendall ES. PYY[3-36]administration decreases the respiratory quotient and reduces adiposity in diet-induced obese mice. J Nutr 2006; 136: 195-201.
127. Baggio LL, Drucker DJ. Clinical endocrinology and metabolism. Glucagon-like peptide-1 and glucagon-like peptide-2. Best Pract Res Clin Endocrinol Metab 2004; 18: 531-554.
128. Drucker DJ. Minireview: The glucagon-like peptides. Endocrinology 2001; 142: 521-527.
129. Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, Schmiegel WH. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997; 273: E981-E988.
130. Miki T, Minami K, Shinozaki H, Matsumura K, Saraya A, Ikeda H, Yamada Y, Holst JJ, Seino S. Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility. Diabetes 2005; 54: 1056-1063.
131. Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1, 7-36: A physiological incretin in man Lancet. 1987:2: 1300-1304.
132. Mojsov S, Weir GC, Habener JF. Insulinotropin: Glucagon-like peptide I (7-37): Co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest 1987; 79: 616-619.
133. Holst JJ, Orskov C, Nielsen OV, Schwartz TW. Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett 1987; 211: 169-174.
134. Balkan B, Li X. Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms. Am J Physiol Regul Integr Comp Physiol 2000; 279: R1449-R1454.
135. Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA 1987; 84: 3434-3438.
136. Fehmann HC, Habener JF. Insulinotropic hormone glucagon-like peptide-I (7-37): Stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. Endocrinology 1992; 130: 159-166.
137. Byrne MM, Gliem K, Wank U, Arnold R, Katschinski M, Polonsky KS, Goke B. Glucagon-like peptide 1 improves the ability of the beta-cell to sense and respond to glucose in subjects with impaired glucose tolerance. Diabetes 1998; 47: 1259-1265.
138. Heller RS, Kieffer TJ, Habener JF. Insulinotropic glucagon-like peptide I receptor expression in glucagon-producing alpha-cells of the rat endocrine pancreas. Diabetes 1997; 46: 785-791.
139. Matsuyama T, Komatsu R, Namba M, Watanabe N, Itoh H, Tarui S. Glucagon-like peptide-1 (7-36 amide): A potent glucagonostatic and insulinotropic hormone. Diabetes Res Clin Pract 1988; 5: 281-284.
140. Morales M, Lopez-Delgado MI, Alcantara A, Luque MA, Clemente F, Marquez L, Puente J, Vinambres C, Malaisse WJ, Villanueva-Penacarrillo ML, Valverde I. Preserved GLP-I effects on glycogen synthase a activity and glucose metabolism in isolated hepatocytes and skeletal muscle from diabetic rats. Diabetes 1997; 46: 1264-1269.
141. Egan JM, Montrose-Rafizadeh C, Wang Y, Bernier M, Roth J. Glucagon-like peptide-1 (7-36): Amide (GLP-1) enhances insulin-stimulated glucose metabolism in 3T3-L1 adipocytes: One of several potential extrapancreatic sites of GLP-1 action. Endocrinology 1994; 135: 2070-2075.
142. D'Alessio DA, Kahn SE, Leusner CR, Ensinck JW. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest 1994; 93: 2263-2266.
143. Meneilly GS, Mcintosh CH, Pederson RA, Habener JF, Gingerich R, Egan JM, Finegood DT, Elahi D. Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes. Diabetes Care 2001; 24: 1951-1956.
144. Baggio LL, Huang Q, Brown TJ, Drucker DJ. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 2004; 127: 546-558.
145. Flint A, Raben A, Rehfeld JF, Holst JJ, Astrup A. The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans. Int J Obes Relat Metab Disord 2000; 24: 288-298.
146. Iltz JL, Baker DE, Setter SM, Keith CR. Exenatide: An incretin mimetic for the treatment of type 2 diabetes mellitus. Clin Ther 2006; 28: 652-665.
147. Lovshin J, Drucker DJ. Synthesis, secretion and biological actions of the glucagon-like peptides. Pediatr Diabetes 2000; 1: 49-57.
148. Pellissier S, Sasaki K, Le Nguyen D, Bataille D, Jarrousse C. Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine. Neurogastroenterol Motil 2004; 16: 455-463.
149. Dubrasquet M, Bataille D, Gespach C. Oxyntomodulin (glucagon-37 or bioactive enteroglucagon): A potent inhibitor of pentagastrin-stimulated acid secretion in rats. Biosci Rep 1982; 2: 391-395.
150. Schjoldager BT, Baldissera FG, Mortensen PE, Holst JJ, Christiansen J. Oxyntomodulin: A potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man. Eur J Clin Invest 1988; 18: 499-503.
151. Wynne K, Park AJ, Small CJ, Patterson M, Ellis SM, Murphy KG, Wren AM, Frost GS, Meeran K, Ghatei MA, Bloom SR. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: A double-blind, randomized, controlled trial. Diabetes 2005; 54: 2390-2395.
152. Meier JJ, Goetze O, Anstipp J, Hagemann D, Holst JJ, Schmidt WE, Gallwitz B, Nauck MA. Gastric inhibitory polypeptide does not inhibit gastric emptying in humans. Am J Physiol Endocrinol Metab 2004; 286: E621-E625.
153. Creutzfeldt W, Ebert R, Willms B, Frerichs H, Brown JC. Gastric inhibitory polypeptide (GIP) and insulin in obesity: Increased response to stimulation and defective feedback control of serum levels. Diabetologia 1978; 14: 15-24.
154. Flatt PR, Bailey CJ, Kwasowski P, Swanston-Flatt SK, Marks V. Abnormalities of GIP in spontaneous syndromes of obesity and diabetes in mice. Diabetes 1983; 32: 433-435.
155. Miyawaki K, Yamada Y, Yano H, Niwa H, Ban N, Ihara Y, Kubota A, Fujimoto S, Kajikawa M, Kuroe A, Tsuda K, Hashimoto H, Yamashita T, Jomori T, Tashiro F, Miyazaki J, Seino Y. Glucose intolerance caused by a defect in the entero-insular axis: A study in gastric inhibitory polypeptide receptor knockout mice. Proc Natl Acad Sci USA 1999; 96: 14843-14847.
156. Starich GH, Bar RS, Mazzaferri EL. GIP increases insulin receptor affinity and cellular sensitivity in adipocytes. Am J Physiol 1985; 249: E603-E607.
157. Gault VA, Irwin N, Green BD, Mccluskey JT, Greer B, Bailey CJ, Harriott P, O'Harte FP, Flatt PR. Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3) GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. Diabetes 2005; 54: 2436-2446.
158. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 2002; 8: 738-742.
159. Yamada Y, Seino Y. Physiology of GIP - a lesson from GIP receptor knockout mice. Horm Metab Res 2004; 36: 771-774.
160. Nonaka N, Shioda S, Niehoff ML, Banks WA. Characterization of blood-brain barrier permeability to PYY3-36 in the mouse. J Pharmacol Exp Ther 2003; 306: 948-953.
161. Banks WA, Tschop M, Robinson SM, Heiman ML. Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 2002; 302: 822-827.
162. Schwartz GJ. The role of gastrointestinal vagal afferents in the control of food intake: Current prospects. Nutrition 2000; 16: 866-873.
163. Uyama N, Geerts A, Reynaert H. Neural connections between the hypothalamus and the liver. Anat Rec A Discov Mol Cell Evol Biol 2004; 280: 808-820.
164. Kreier F, Fliers E, Voshol PJ, Van Eden CG, Havekes LM, Kalsbeek A, Van Heijningen CL, Sluiter AA, Mettenleiter TC, Romijn JA, Sauerwein HP, Buijs RM. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat -functional implications. J Clin Invest 2002; 110: 1243-1250.
165. Lam TK, Pocai A, Gutierrez-Juarez R, Obici S, Bryan J, Aguilar-Bryan L, Schwartz GJ, Rossetti L. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med 2005; 11: 320-327.
166. Tolle V, Bassant MH, Zizzari P, Poindessous-Jazat F, Tomasetto C, Epelbaum J, Bluet-Pajot MT. Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats. Endocrinology 2002; 143: 1353-1361.
167. Thompson JC, Fender HR, Ramus NI, Villar HV, Rayford PL. Cholecystokinin metabolism in man and dogs. Ann Surg 1975; 182: 496-504.
168. Hoffmann P, Eberlein GA, Reeve JR Jr, Bunte RH, Grandt D, Goebell H, Eysselein VE. Comparison of clearance and metabolism of infused cholecystokinins 8 and 58 in dogs. Gastroenterology 1993; 105: 1732-1736.
169. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V. Glucagon-like peptide-1 (7-36): Amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: Acute post-prandial and 24-h secretion patterns. J Endocrinol 1993; 138: 159-166.
170. Hui H, Farilla L, Merkel P, Perfetti R. The short half-life of glucagon-like peptide-1 in plasma does not reflect its long-lasting beneficial effects. Eur J Endocrinol 2002; 146: 863-869.
171. Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985; 89: 1070-1077.
172. Shechter Y, Tsubery H, Mironchik M, Rubinstein M, Fridkin M. Reversible PEGylation of peptide YY3-36 prolongs its inhibition of food intake in mice. FEBS Lett 2005; 579: 2439-2444.
173. Kervran A, Dubrasquet M, Blache P, Martinez J, Bataille D. Metabolic clearance rates of oxyntomodulin and glucagon in the rat: Contribution of the kidney. Regul Pept 1990; 31: 41-52.
174. Sarson DL, Hayter RC, Bloom SR. The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide (GIP) in man. Eur J Clin Invest 1982; 12: 457-461.