Hormonal signaling in the gut

Journal of Biological Chemistry

Volumn 289, Issue 17, 2014, Pages 11642-11649

  Côté, Clémence D ^a,b   Zadeh Tahmasebi, Melika ^a,b   Rasmussen, Brittany A ^a,b   Duca, Frank A ^a,b   Lam, Tony K T ^a,b  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; NUTRIENTS;

ANTIDIABETIC EFFECTS; GLUCOSE CONTROL; GLUCOSE PRODUCTION; GLYCEMIA; GUT HORMONES; HORMONAL SIGNALING;

HORMONES;

CHOLECYSTOKININ; CHOLECYSTOKININ A RECEPTOR; COLESEVELAM; CYCLIC AMP DEPENDENT PROTEIN KINASE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; LEPTIN; LEPTIN RECEPTOR; LIRAGLUTIDE; LONG CHAIN FATTY ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE C DELTA;

CELLULAR, SUBCELLULAR AND MOLECULAR BIOLOGICAL PHENOMENA AND FUNCTIONS; DRUG TARGETING; DUODENAL JEJUNAL BYPASS; DUODENUM; FEEDBACK SYSTEM; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCEMIC CONTROL; HORMONAL REGULATION; HORMONAL SIGNALING; HORMONE RECEPTOR INTERACTION; HORMONE RELEASE; HUMAN; INTESTINE; INTESTINE ABSORPTION; INTESTINE BYPASS; JEJUNUM; MOLECULAR DYNAMICS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUTRIENT SENSING; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STOMACH BYPASS;

BARIATRIC SURGERY; DIABETES; FATTY ACID; FOOD INTAKE; GLUCOSE METABOLISM; HORMONES; INTESTINE;

GASTROINTESTINAL HORMONES; HUMANS; SIGNAL TRANSDUCTION; STOMACH;

EID: 84899422445     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.O114.556068     Document Type: Review

References (100)

1. Scully, T. (2012) Diabetes in numbers. Nature 485, S2-S3
2. Stagnitti, M. N. (2001) Statistical Brief # 34 The Prevalence of Obesity and Other Chronic Health Conditions among Diabetic Adults in the U. S. Community Population, 2001, Medical Expenditure Panel Survey (MEPS), pp. 5-9, Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, Rockville, MD
3. Speakman, J. R., and O'Rahilly, S. (2012) Fat: an evolving issue. Dis. Model. Mech. 5, 569-573
4. Clark, C. M., Jr. (1998) The burden of chronic hyperglycemia. Diabetes Care 21, Suppl. 3, C32-C34
5. Rojas, L. B., and Gomes, M. B. (2013) Metformin: an old but still the best treatment for type 2 diabetes. Diabetol. Metab. Syndr. 5, 6
6. Drazen, D. L., Vahl, T. P., D'Alessio, D. A., Seeley, R. J., and Woods, S. C. (2006) Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. Endocrinology 147, 23-30
7. Cummings, D. E., Purnell, J. Q., Frayo, R. S., Schmidova, K., Wisse, B. E., and Weigle, D. S. (2001) A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50, 1714-1719 (Pubitemid 33641587)
8. Monteleone, P., Bencivenga, R., Longobardi, N., Serritella, C., and Maj, M. (2003) Differential responses of circulating ghrelin to high-fat or high-carbohydrate meal in healthy women. J. Clin. Endocrinol. Metab. 88, 5510-5514
9. Overduin, J., Frayo, R. S., Grill, H. J., Kaplan, J. M., and Cummings, D. E. (2005) Role of the duodenum and macronutrient type in ghrelin regulation. Endocrinology 146, 845-850
10. Tschöp, M., Smiley, D. L., and Heiman, M. L. (2000) Ghrelin inducesadiposity in rodents. Nature 407, 908-913
11. Wren, A. M., Seal, L. J., Cohen, M. A., Brynes, A. E., Frost, G. S., Murphy,K. G., Dhillo, W. S., Ghatei, M. A., and Bloom, S. R. (2001) Ghrelin enhances appetite and increases food intake in humans. J. Clin. Endocrinol. Metab. 86, 5992
12. Date, Y., Murakami, N., Toshinai, K., Matsukura, S., Niijima, A., Matsuo, H., Kangawa, K., and Nakazato, M. (2002) The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 123, 1120-1128
13. le Roux, C. W., Neary, N. M., Halsey, T. J., Small, C. J., Martinez-Isla, A. M., Ghatei, M. A., Theodorou, N. A., and Bloom, S. R. (2005) Ghrelin does not stimulate food intake in patients with surgical procedures in- volving vagotomy. J. Clin. Endocrinol. Metab. 90, 4521-4524
14. Falkén, Y., Hellström, P. M., Sanger, G. J., Dewit, O., Dukes, G., Grybäck, P., Holst, J. J., and Näslund, E. (2010) Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans. Neurogastroenterol. Motil. 22, e192-e200
15. Reimer, M. K., Pacini, G., and Ahrén, B. (2003) Dose-dependent inhibition by ghrelin of insulin secretion in the mouse. Endocrinology 144, 916-921 (Pubitemid 36262858)
16. Duca, F. A., and Covasa, M. (2012) Current and emerging concepts on the role of peripheral signals in the control of food intake and development of obesity. Br. J. Nutr. 108, 778-793
17. Williams, J. A., and Blevins, G. T. (1993) Cholecystokinin and regulation of pancreatic acinar cell function. Physiol. Rev. 73, 701-723
18. Cheung, G. W., Kokorovic, A., Lam, C. K., Chari, M., and Lam, T. K. (2009) Intestinal cholecystokinin controls glucose production through a neuronal network. Cell Metab. 10, 99-109
19. Sundaresan, S., Shahid, R., Riehl, T. E., Chandra, R., Nassir, F., Stenson, W. F., Liddle, R. A., and Abumrad, N. A. (2013) CD36-dependent signaling mediates fatty acid-induced gut release of secretin and cholecystokinin. FASEB J. 27, 1191-1202
20. Breen, D. M., Yue, J. T., Rasmussen, B. A., Kokorovic, A., Cheung, G. W., and Lam, T. K. (2011) Duodenal PKC-δand cholecystokinin signaling axis regulates glucose production. Diabetes 60, 3148-3153
21. Kokorovic, A., Cheung, G. W., Breen, D. M., Chari, M., Lam, C. K., and Lam, T. K. (2011) Duodenal mucosal protein kinase C-δregulates glucose production in rats. Gastroenterology 141, 1720-1727
22. Raybould, H. E., Gayton, R. J., and Dockray, G. J. (1988) Mechanisms of action of peripherally administered cholecystokinin octapeptide on brain stem neurons in the rat. J. Neurosci. 8, 3018-3024
23. Rasmussen, B. A., Breen, D. M., Luo, P., Cheung, G. W. C., Yang, C. S., Sun, B., Kokorovic, A., Rong, W., and Lam, T. K. (2012) Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats. Gastroenterology 142, 834-843.e3
24. Wang, P. Y., Caspi, L., Lam, C. K., Chari, M., Li, X., Light, P. E., Gutierrez- Juarez, R., Ang, M., Schwartz, G. J., and Lam, T. K. (2008) Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production. Nature 452, 1012-1016
25. Marina, A. L., Utzschneider, K. M., Wright, L. A., Montgomery, B. K., Marcovina, S. M., and Kahn, S. E. (2012) Colesevelam improves oral but not intravenous glucose tolerance by a mechanism independent of insulin sensitivity and β-cell function. Diabetes Care 35, 1119-1125
26. Rocca, A. S., and Brubaker, P. L. (1999) Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 140, 1687-1694
27. Theodorakis, M. J., Carlson, O., Michopoulos, S., Doyle, M. E., Juhaszova, M., Petraki, K., and Egan, J. M. (2006) Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am. J. Physiol.Endocrinol. Metab. 290, E550-E559
28. Habib, A. M., Richards, P., Cairns, L. S., Rogers, G. J., Bannon, C. A., Parker, H. E., Morley, T. C., Yeo, G. S., Reimann, F., and Gribble, F. M. (2012) Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology153, 3054-3065
29. Layer, P., Holst, J. J., Grandt, D., and Goebell, H. (1995) Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig. Dis. Sci. 40, 1074-1082
30. Tolhurst, G., Reimann, F., and Gribble, F. M. (2012) Intestinal sensing of nutrients. Handb. Exp. Pharmacol. 209, 309-335
31. Kreymann, B., Williams, G., Ghatei, M. A., and Bloom, S. R. (1987) Glucagon- like peptide-1 7-36: a physiological incretin in man. Lancet 2, 1300-1304
32. Drucker, D. J. (2006) The biology of incretin hormones. Cell Metab. 3, 153-165
33. Holst, J. J., and Deacon, C. F. (2005) Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia 48, 612-615
34. Burcelin, R., Serino, M., and Cabou, C. (2009) A role for the gut-to-brain GLP-1-dependent axis in the control of metabolism. Curr. Opin. Pharmacol.9, 744-752
35. Burcelin, R., Da Costa, A., Drucker, D., and Thorens, B. (2001) Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes 50, 1720-1728 (Pubitemid 33641588)
36. Knauf, C., Cani, P. D., Kim, D. H., Iglesias, M. A., Chabo, C., Waget, A., Colom, A., Rastrelli, S., Delzenne, N. M., Drucker, D. J., Seeley, R. J., and Burcelin, R. (2008) Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing. Diabetes 57, 2603-2612
37. Nishizawa, M., Nakabayashi, H., Uchida, K., Nakagawa, A., and Niijima, A. (1996) The hepatic vagal nerve is receptive to incretin hormone glucagon- like peptide-l, but not to glucose-dependent insulinotropic polypeptide, in the portal vein. J. Auton. Nerv. Syst. 61, 149-154
38. Balkan, B., and Li, X. (2000) Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, R1449-R1454
39. Johnson, K. M., Edgerton, D. S., Rodewald, T., Scott, M., Farmer, B., Neal, D., and Cherrington, A. D. (2008) Intraportally delivered GLP-1, in the presence of hyperglycemia induced via peripheral glucose infusion, does not change whole body glucose utilization. Am. J. Physiol. Endocrinol.Metab. 294, E380-E384
40. Hayes, M. R., Kanoski, S. E., De Jonghe, B. C., Leichner, T. M., Alhadeff, A. L., Fortin, S. M., Arnold, M., Langhans, W., and Grill, H. J. (2011) The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1. Am. J. Physiol. Regul Integr. Comp. Physiol. 301, R1479-R1485
41. Vollmer, K., Holst, J. J., Baller, B., Ellrichmann, M., Nauck, M. A., Schmidt, W. E., and Meier, J. J. (2008) Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance.Diabetes 57, 678-687
42. Lovshin, J. A., and Drucker, D. J. (2009) Incretin-based therapies for type2 diabetes mellitus. Nat. Rev. Endocrinol. 5, 262-269
43. Waget, A., Cabou, C., Masseboeuf, M., Cattan, P., Armanet, M., Karaca, M., Castel, J., Garret, C., Payros, G., Maida, A., Sulpice, T., Holst, J. J., Drucker, D. J., Magnan, C., and Burcelin, R. (2011) Physiological and pharmacological mechanisms through which the DPP-4 inhibitor sitagliptin regulates glycemia in mice. Endocrinology 152, 3018-3029
44. Mingrone, G., and Castagneto-Gissey, L. (2009) Mechanisms of early improvement/resolution of type 2 diabetes after bariatric surgery. Diabetes Metab. 35, 518-523
45. Rodieux, F., Giusti, V., D'Alessio, D. A., Suter, M., and Tappy, L. (2008) Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release. Obesity (Silver Spring). 16, 298-305 (Pubitemid 351271908)
46. Chambers, A. P., Jessen, L., Ryan, K. K., Sisley, S., Wilson-Pérez, H. E., Stefater, M. A., Gaitonde, S. G., Sorrell, J. E., Toure, M., Berger, J., D'Alessio, D. A., Woods, S. C., Seeley, R. J., and Sandoval, D. A. (2011) Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 141,950-958
47. Habegger, K. M., Heppner, K. M., Amburgy, S. E., Ottaway, N., Holland,J., Raver, C., Bartley, E., Müller, T. D., Pfluger, P. T., Berger, J., Toure, M., Benoit, S. C., Dimarchi, R. D., Perez-Tilve, D., D'Alessio, D. A., Seeley, R. J., and Tschöp, M. H. (2014) GLP-1R responsiveness predicts individual gastric bypass efficacy on glucose tolerance in rats. Diabetes 63,505-513
48. Wilson-Pérez, H. E., Chambers, A. P., Ryan, K. K., Li, B., Sandoval, D. A., Stoffers, D., Drucker, D. J., Pérez-Tilve, D., and Seeley, R. J. (2013) Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon- like peptide 1 receptor deficiency. Diabetes 62, 2380-2385
49. Mokadem, M., Zechner, J. F., Margolskee, R. F., Drucker, D. J., and Aguirre,V. (2013) Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagonlike peptide-1 deficiency. Mol. Metab. 10.1016/j.molmet.2013.11.010
50. Breen, D. M., Rasmussen, B. A., Kokorovic, A., Wang, R., Cheung, G. W., and Lam, T. K. (2012) Jejunal nutrient sensing is required for duodenaljejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nat. Med. 18, 950-955
51. Pacheco, D., de Luis, D. A., Romero, A., González Sagrado, M., Conde, R., Izaola, O., Aller, R., and Delgado, A. (2007) The effects of duodenal- jejunal exclusion on hormonal regulation of glucose metabolism inGoto-Kakizaki rats. Am. J. Surg. 194, 221-224
52. Jiao, J., Bae, E. J., Bandyopadhyay, G., Oliver, J., Marathe, C., Chen, M., Hsu, J. Y., Chen, Y., Tian, H., Olefsky, J. M., and Saberi, M. (2013) Restoration of euglycemia after duodenal bypass surgery is reliant on central and peripheral inputs in Zucker fa/fa rats. Diabetes 62, 1074-1083
53. Bojsen-Møller, K. N., Dirksen, C. Jørgensen, N. B., Jacobsen, S. H., Serup, A. K., Albers, P. H., Hansen, D. L., Worm, D., Naver, L., Kristiansen, V. B., Wojtaszewski, J. F., Kiens, B., Holst, J. J., Richter, E. A., and Madsbad, S. (2013) Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass.Diabetes 10.2337/db13-1307
54. Zhang, S. Y., Sun, X. J., Zheng, J. B., Wang, W., Liu, D., Chen, N. Z., He, S., Huo, X. W., and Smith, W. (2014) Preserve common limb in duodenaljejunal bypass surgery benefits rats with type 2-like diabetes. Obes. Surg.24, 405-411
55. Salinari, S., le Roux, C. W., Bertuzzi, A., Rubino, F., and Mingrone, G. (2014) Duodenal-jejunal bypass and jejunectomy improve insulin sensitivity in Goto-Kakizaki diabetic rats without changes in incretins or insulin secretion. Diabetes 63, 1069-1078
56. Rubino, F., Moo, T. A., Rosen, D. J., Dakin, G. F., and Pomp, A. (2009) Diabetes surgery: a new approach to an old disease. Diabetes Care 32, Suppl. 2, S368-S372
57. Bradley, D., Magkos, F., and Klein, S. (2012) Effects of bariatric surgery on glucose homeostasis and type 2 diabetes. Gastroenterology 143, 897-912
58. Rubino, F., R'bibo, S. L., del Genio, F., Mazumdar, M., and McGraw, T. E. (2010) Metabolic surgery: the role of the gastrointestinal tract in diabetes mellitus. Nat. Rev. Endocrinol. 6, 102-109
59. Cohen, R. V., Pinheiro, J. C., Schiavon, C. A., Salles, J. E., Wajchenberg, B. L., and Cummings, D. E. (2012) Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care 35,1420-1428
60. Schauer, P. R., Kashyap, S. R., Wolski, K., Brethauer, S. A., Kirwan, J. P., Pothier, C. E., Thomas, S., Abood, B., Nissen, S. E., and Bhatt, D. L. (2012) Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N. Engl. J. Med. 366, 1567-1576
61. Mingrone, G., Panunzi, S., De Gaetano, A., Guidone, C., Iaconelli, A., Leccesi, L., Nanni, G., Pomp, A., Castagneto, M., Ghirlanda, G., and Rubino, F. (2012) Bariatric surgery versus conventional medical therapy for type 2 diabetes. N. Engl. J. Med. 366, 1577-1585
62. Rubino, F., and Marescaux, J. (2004) Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann. Surg. 239, 1-11
63. Geloneze, B., Geloneze, S. R., Chaim, E., Hirsch, F. F., Felici, A. C., Lambert, G., Tambascia, M. A., and Pareja, J. C. (2012) Metabolic surgery for non-obese type 2 diabetes: incretins, adipocytokines, and insulin secretion/ resistance changes in a 1-year interventional clinical controlledstudy. Ann. Surg. 256, 72-78
64. 2: a report of 2 cases. Surg. Obes. Relat. Dis. 3, 195-197
65. Cohen, R., Caravatto, P. P., Correa, J. L., Noujaim, P., Petry, T. Z., Salles, J. E., and Schiavon, C. A. (2012) Glycemic control after stomach-sparing duodenal-jejunal bypass surgery in diabetic patients with low body mass index. Surg. Obes. Relat. Dis. 8, 375-380
66. Lee, H. C., Kim, M. K., Kwon, H. S., Kim, E., and Song, K. H. (2010) Early changes in incretin secretion after laparoscopic duodenal-jejunal bypass surgery in type 2 diabetic patients. Obes. Surg. 20, 1530-1535
67. Light, P. E., Manning Fox, J. E., Riedel, M. J., and Wheeler, M. B. (2002) Glucagon-like peptide-1 inhibits pancreatic ATP-sensitive potassium channels via a protein kinase A- and ADP-dependent mechanism. Mol. Endocrinol. 16, 2135-2144
68. Rupprecht, L. E., Mietlicki-Baase, E. G., Zimmer, D. J., McGrath, L. E., Olivos, D. R., and Hayes, M. R. (2013) Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt. Am. J. Physiol. Endocrinol. Metab. 305, E751-E759
69. Sutton, G. M., Patterson, L. M., and Berthoud, H.-R. (2004) Extracellular signal-regulated kinase 1/2 signaling pathway in solitary nucleus mediates cholecystokinin-induced suppression of food intake in rats. J. Neurosci. 24, 10240-10247 (Pubitemid 39492051)
70. Williams, J. A., Sans, M. D., Tashiro, M., Schäfer, C., Bragado, M. J., and Dabrowski, A. (2002) Cholecystokinin activates a variety of intracellular signal transduction mechanisms in rodent pancreatic acinar cells. Pharmacol. Toxicol. 91, 297-303
71. Bado, A., Levasseur, S., Attoub, S., Kermorgant, S., Laigneau, J. P., Bortoluzzi, M. N., Moizo, L., Lehy, T., Guerre-Millo, M., Le Marchand- Brustel, Y., and Lewin, M. J. (1998) The stomach is a source of leptin.Nature 394, 790-793
72. Cinti, S., Matteis, R. D., Picó, C., Ceresi, E., Obrador, A., Maffeis, C., Oliver, J., and Palou, A. (2000) Secretory granules of endocrine and chief cells of human stomach mucosa contain leptin. Int. J. Obes. Relat. Metab. Disord. 24, 789-793
73. Guilmeau, S., Buyse, M., and Tsocas, A., Laigneau, J. P., and Bado, A. (2003) Duodenal leptin stimulates cholecystokinin secretion: evidence of a positive leptin-cholecystokinin feedback loop. Diabetes 52, 1664-1672
74. Cammisotto, P. G., Renaud, C., Gingras, D., Delvin, E., Levy, E., and Bendayan, M. (2005) Endocrine and exocrine secretion of leptin by the gastric mucosa. J. Histochem. Cytochem. 53, 851-860
75. Cammisotto, P. G., Gingras, D., Renaud, C., Levy, E., and Bendayan, M. (2006) Secretion of soluble leptin receptors by exocrine and endocrine cells of the gastric mucosa. Am. J. Physiol. Gastrointest. Liver. Physiol. 290, G242-G2493
76. Cammisotto, P., and Bendayan, M. (2012) A review on gastric leptin: the exocrine secretion of a gastric hormone. Anat. Cell Biol. 45, 1-16
77. Sobhani, I., Bado, A., Vissuzaine, C., Buyse, M., Kermorgant, S., Laigneau, J. P., Attoub, S., Lehy, T., Henin, D., Mignon, M., and Lewin, M. J. (2000) Leptin secretion and leptin receptor in the human stomach. Gut 47,178-183 (Pubitemid 30489759)
78. Zastrow, O., Seidel, B., Kiess, W., Thiery, J., Keller, E., Böttner, A., and Kratzsch, J. (2003) The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int. J. Obes. Relat. Metab. Disord. 27, 1472-1478
79. Yang, G., Ge, H., Boucher, A., Yu, X., and Li, C. (2004) Modulation of direct leptin signaling by soluble leptin receptor. Mol. Endocrinol. 18, 1354-1362
80. Mix, H., Widjaja, A., Jandl, O., Cornberg, M., Kaul, A., Göke, M., Beil, W., Kuske, M., Brabant, G., Manns, M. P., and Wagner, S. (2000) Expression of leptin and leptin receptor isoforms in the human stomach. Gut 47,481-486
81. Buyse, M., Ovesjö, M. L., Goïot, H., Guilmeau, S., Péranzi, G., Moizo, L., Walker, F., Lewin, M. J., Meister, B., and Bado, A. (2001) Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve. Eur. J. Neurosci. 14, 64-72
82. Barrenetxe, J., Villaro, A. C., Guembe, L., Pascual, I., Muñoz-Navas, M., Barber, A., and Lostao, M. P. (2002) Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes. Gut 50, 797-802 (Pubitemid 34539041)
83. Morton, N. M., Emilsson, V., Liu, Y. L., and Cawthorne, M. A. (1998) Leptin action in intestinal cells. J. Biol. Chem. 273, 26194-26201
84. Iqbal, J., Li, X., Chang, B. H. J., Chan, L., Schwartz, G. J., Chua, S. C., Jr., and Hussain, M. M. (2010) An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption. J. Lipid Res. 51, 1929-1942
85. Ducroc, R., Guilmeau, S., Akasbi, K., Devaud, H., Buyse, M., and Bado, A. (2005) Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1. Diabetes54, 348-354
86. Buettner, C., Pocai, A., Muse, E. D., Etgen, A. M., Myers, M. G., Jr., and Rossetti, L. (2006) Critical role of STAT3 in leptin's metabolic actions. Cell Metab. 4, 49-60 (Pubitemid 43942253)
87. Kievit, P., Howard, J. K., Badman, M. K., Balthasar, N., Coppari, R., Mori, H., Lee, C. E., Elmquist, J. K., Yoshimura, A., and Flier, J. S. (2006) Enhanced leptin sensitivity and improved glucose homeostasis in mice lack- ing suppressor of cytokine signaling-3 in POMC-expressing cells. Cell Metab 4, 123-132 (Pubitemid 44138722)
88. Morton, G. J., Gelling, R. W., Niswender, K. D., Morrison, C. D., Rhodes, C. J., and Schwartz, M. W. (2005) Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab. 2, 411-420
89. Wang, M. Y., Chen, L., Clark, G. O., Lee, Y., Stevens, R. D., Ilkayeva, O. R., Wenner, B. R., Bain, J. R., Charron, M. J., Newgard, C. B., and Unger, R. H. (2010) Leptin therapy in insulin-deficient type I diabetes. Proc. Natl.Acad. Sci. U.S.A. 107, 4813-4819
90. Yu, X., Park, B. H., Wang, M. Y., Wang, Z. V., and Unger, R. H. (2008) Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc. Natl. Acad. Sci. U.S.A. 105, 14070-14075
91. Chinookoswong, N., Wang, J. L., and Shi, Z. Q. (1999) Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes 48, 1487-1492
92. German, J. P., Thaler, J. P., Wisse, B. E., Oh-I, S., Sarruf, D. A., Matsen, M. E., Fischer, J. D., Taborsky, G. J., Jr., Schwartz, M. W., and Morton, G. J. (2011) Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology152, 394-404
93. Fujikawa, T., Berglund, E. D., Patel, V. R., Ramadori, G., Vianna, C. R., Vong, L., Thorel, F., Chera, S., Herrera, P. L., Lowell, B. B., Elmquist, J. K., Baldi, P., and Coppari, R. (2013) Leptin engages a hypothalamic neurocircuitry to permit survival in the absence of insulin. Cell Metab. 18,431-444
94. El Homsi, M., Ducroc, R., Claustre, J., Jourdan, G., Gertler, A., Estienne, M., Bado, A., Scoazec, J. Y., and Plaisancié, P. (2007) Leptin modulates the expression of secreted and membrane-associated mucins in colonic epithelial cells by targeting PKC, PI3K, andMAPKpathways. Am. J. Physiol. Gastrointest Liver Physiol. 293, G365-G373
95. Guo, X., Roberts, M. R., Becker, S. M., Podd, B., Zhang, Y., Chua, S. C., Jr., Myers, M. G., Jr., Duggal, P., Houpt, E. R., and Petri, W. A., Jr. (2011) Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolytica. Mucosal Immunol. 4, 294-303
96. Rasmussen, B. A., Breen, D. M., Duca, F. A., Côté, C. D., Zadeh-Tahmasebi, M., Filippi, B. M., and Lam, T. K. (2014) Jejunal leptin-PI3K signaling lowers glucose production. Cell Metab. 19, 155-161
97. Rasmussen, B. A., Breen, D. M., and Lam, T. K. (2012) Lipid sensing in the gut, brain and liver. Trends Endocrinol. Metab. 23, 49-55
98. Breen, D. M., Rasmussen, B. A., Côté, C. D., Jackson, V. M., and Lam, T. K. (2013) Nutrient-sensing mechanisms in the gut as therapeutic targets for diabetes. Diabetes 62, 3005-3013
99. Li, Y., Wu, X., Zhou, S., and Owyang, C. (2011) Low-affinity CCK-A receptors are coexpressed with leptin receptors in rat nodose ganglia: implications for leptin as a regulator of short-term satiety. Am. J. Gastrointest Liver Physiol. 300, G217-G227
100. Schwartz, M. W., Seeley, R. J., Tschöp, M. H., Woods, S. C., Morton, G. J., Myers, M. G., and D'Alessio, D. (2013) Cooperation between brain and islet in glucose homeostasis and diabetes. Nature 503, 59-66