From gut changes to type 2 diabetes remission after gastric bypass surgeries

Abstract

Increasing evidence suggests that the gut may influence the host’s metabolism and ultimately change the outcomes of type 2 diabetes mellitus (T2DM). We review the evidence on the relationship between the gut and T2DM remission after gastric bypass surgery, and discuss the potential mechanisms underlying the above relationship: gut anatomical rearrangement, microbial composition changes, altered gut cells, and gut hormone modulation. However, the exact changes and their relative importance in the metabolic improvements after gastric bypass surgery remain to be further clarified. Elucidating the precise metabolic mechanisms of T2DM resolution after bypass surgery will help to reveal the molecular mechanisms of pathogenesis, and facilitate the development of novel diagnoses and preventative interventions for this common disease.

Keywords

gastric bypass / T2DM / gut

References

[1] Huang ES, Basu A, O’Grady M, Capretta JC. Projecting the future diabetes population size and related costs for the U.S. Diabetes Care2009; 32(12): 2225-2229

[2] Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care2004; 27(5): 1047-1053

[3] Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE; the Diabetes Prevention Program Research Group. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet2012; 379(9833): 2243-2251

[4] Hamman RF. Genetic and environmental determinants of non-insulin-dependent diabetes mellitus (NIDDM). Diabetes Metab Rev1992; 8(4): 287-338

[5] Polonsky KS, Sturis J, Bell GI. Seminars in Medicine of the Beth Israel Hospital, Boston. Non-insulin-dependent diabetes mellitus- a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med1996; 334(12): 777-783

[6] James PT, Leach R, Kalamara E, Shayeghi M. The worldwide obesity epidemic. Obes Res2001; 9(Suppl 4): 228S-233S

[7] Brolin RE. Bariatric surgery and long-term control of morbid obesity. JAMA2002; 288(22): 2793-2796

[8] Fisher BL, Schauer P. Medical and surgical options in the treatment of severe obesity. Am J Surg2002; 184(6 Supplement 2): 9S-16S

[9] Martins C, Strømmen M, Stavne OA, Nossum R, Mårvik R, Kulseng B. Bariatric surgery versus lifestyle interventions for morbid obesity—changes in body weight, risk factors and comorbidities at 1 year. Obes Surg2011; 21(7): 841-849

[10] Jørgensen NB, Jacobsen SH, Dirksen C, Bojsen-Møller KN, Naver L, Hvolris L, Clausen TR, Wulff BS, Worm D, Lindqvist Hansen D, Madsbad S, Holst JJ. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with type 2 diabetes and normal glucose tolerance. Am J Physiol Endocrinol Metab2012; 303(1): E122-E131

[11] Cohen RV, Pinheiro JC, Schiavon CA, Salles JE, Wajchenberg BL, Cummings DE. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care2012; 35(7): 1420-1428

[12] Dixon JB, le Roux CW, Rubino F, Zimmet P. Bariatric surgery for type 2 diabetes. Lancet2012; 379(9833): 2300-2311

[13] Carlsson LM, Peltonen M, Ahlin S, Anveden Å, Bouchard C, Carlsson B, Jacobson P, Lönroth H, Maglio C, Näslund I, Pirazzi C, Romeo S, Sjöholm K, Sjöström E, Wedel H, Svensson PA, Sjöström L. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med2012; 367(8): 695-704

[14] Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science2005; 307(5717): 1909-1914

[15] Schauer PR, Ikramuddin S, Gourash W, Ramanathan R, Luketich J. Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Ann Surg2000; 232(4): 515-529

[16] Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM, Dohm L. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg1995; 222(3): 339-352

[17] Scopinaro N, Adami GF, Marinari GM, Gianetta E, Traverso E, Friedman D, Camerini G, Baschieri G, Simonelli A. Biliopancreatic diversion. World J Surg1998; 22(9): 936-946

[18] Elder KA, Wolfe BM. Bariatric surgery: a review of procedures and outcomes. Gastroenterology2007; 132(6): 2253-2271

[19] Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab2004; 89(6): 2608-2615

[20] Rubino F, R’bibo SL, del Genio F, Mazumdar M, McGraw TE. Metabolic surgery: the role of the gastrointestinal tract in diabetes mellitus. Nat Rev Endocrinol2010; 6(2): 102-109

[21] Boza C, Muñoz R, Yung E, Milone L, Gagner M. Sleeve gastrectomy with ileal transposition (SGIT) induces a significant weight loss and diabetes improvement without exclusion of the proximal intestine. J Gastrointest Surg2011; 15(6): 928-934

[22] Escalona A, Yáñez R, Pimentel F, Galvao M, Ramos AC, Turiel D, Boza C, Awruch D, Gersin K, Ibáñez L. Initial human experience with restrictive duodenal-jejunal bypass liner for treatment of morbid obesity. Surg Obes Relat Dis2010; 6(2): 126-131

[23] Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature2006; 444(7121): 854-859

[24] Coll AP, Farooqi IS, O’Rahilly S. The hormonal control of food intake. Cell2007; 129(2): 251-262

[25] Lam TKT. Neuronal regulation of homeostasis by nutrient sensing. Nat Med2010; 16(4): 392-395

[26] Imeryüz N, Yeğen BÇ, Bozkurt A, Coşkun T, Villanueva-Peñacarrillo ML, Ulusoy NB. Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol1997; 273(4 Pt 1): G920-G927

[27] Drewe J, Gadient A, Rovati LC, Beglinger C. Role of circulating cholecystokinin in control of fat-induced inhibition of food intake in humans. Gastroenterology1992; 102(5): 1654-1659

[28] Ogawa N, Yamaguchi H, Shimbara T, Toshinai K, Kakutani M, Yonemori F, Nakazato M. The vagal afferent pathway does not play a major role in the induction of satiety by intestinal fatty acid in rats. Neurosci Lett2008; 433(1): 38-42

[29] Breen DM, Rasmussen BA, Kokorovic A, Wang R, Cheung GWC, Lam TKT. Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes. Nat Med2012; 18(6): 950-955

[30] Hansen EN, Tamboli RA, Isbell JM, Saliba J, Dunn JP, Marks-Shulman PA, Abumrad NN. Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery. Am J Physiol Gastrointest Liver Physiol2011; 300(5): G795-G802

[31] Gaitonde S, Kohli R, Seeley R. The role of the gut hormone GLP-1 in the metabolic improvements caused by ileal transposition. J Surg Res2012; 178(1): 33-39

[32] Boza C, Gagner M, Devaud N, Escalona A, Muñoz R, Gandarillas M. Laparoscopic sleeve gastrectomy with ileal transposition (SGIT): A new surgical procedure as effective as gastric bypass for weight control in a porcine model. Surg Endosc2008; 22(4): 1029-1034

[33] Strader AD, Vahl TP, Jandacek RJ, Woods SC, D’Alessio DA, Seeley RJ. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab2005; 288(2): E447-E453

[34] Mason EE. Ilial transposition and enteroglucagon/GLP-1 in obesity (and diabetic?) surgery. Obes Surg1999; 9(3): 223-228

[35] Holst JJ. Glucagon-like peptide 1 (GLP-1): an intestinal hormone, signalling nutritional abundance, with an unusual therapeutic potential. Trends Endocrinol Metab1999; 10(6): 229-235

[36] Bullock BP, Heller RS, Habener JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology1996; 137(7): 2968-2978

[37] Patti ME, Houten SM, Bianco AC, Bernier R, Larsen PR, Holst JJ, Badman MK, Maratos-Flier E, Mun EC, Pihlajamaki J, Auwerx J, Goldfine AB. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring)2009; 17(9): 1671-1677

[38] Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science2001; 294(5548): 1866-1870

[39] Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab2009; 10(3): 167-177

[40] Pournaras DJ, Glicksman C, Vincent RP, Kuganolipava S, Alaghband-Zadeh J, Mahon D, Bekker JHR, Ghatei MA, Bloom SR, Walters JRF, Welbourn R, le Roux CW. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology2012; 153(8): 3613-3619

[41] Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun2005; 329(1): 386-390

[42] Mithieux G. The new functions of the gut in the control of glucose homeostasis. Curr Opin Clin Nutr Metab Care2005; 8(4): 445-449

[43] Troy S, Soty M, Ribeiro L, Laval L, Migrenne S, Fioramonti X, Pillot B, Fauveau V, Aubert R, Viollet B, Foretz M, Leclerc J, Duchampt A, Zitoun C, Thorens B, Magnan C, Mithieux G, Andreelli F. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice. Cell Metab2008; 8(3): 201-211

[44] Kashyap SR, Daud S, Kelly KR, Gastaldelli A, Win H, Brethauer S, Kirwan JP, Schauer PR. Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes. Int J Obes (Lond)2010; 34(3): 462-471

[45] Hayes MT, Foo J, Besic V, Tychinskaya Y, Stubbs RS. Is intestinal gluconeogenesis a key factor in the early changes in glucose homeostasis following gastric bypass? Obes Surg2011; 21(6): 759-762

[46] Consortium THMP. Structure, function and diversity of the healthy human microbiome. Nature2012; 486(7402): 207-214

[47] Musso G, Gambino R, Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu Rev Med2011; 62(1): 361-380

[48] Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol2007; 73(4): 1073-1078

[49] Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA2004; 101(44): 15718-15723

[50] Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA2008; 105(43): 16767-16772

[51] Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature2006; 444(7122): 1022-1023

[52] Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik-Brown R. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA2009; 106(7): 2365-2370

[53] Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, Flint HJ. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond)2008; 32(11): 1720-1724

[54] Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science2010; 328(5975): 228-231

[55] Wei X, Yang Z, Rey FE, Ridaura VK, Davidson NO, Gordon JI, Semenkovich CF. Fatty acid synthase modulates intestinal barrier function through palmitoylation of mucin 2. Cell Host Microbe2012; 11(2): 140-152

[56] Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science2005; 308(5728): 1635-1638

[57] Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature2009; 457(7228): 480-484

[58] Santacruz A, Marcos A, Wärnberg J, Martí A, Martin-Matillas M, Campoy C, Moreno LA, Veiga O, Redondo-Figuero C, Garagorri JM, Azcona C, Delgado M, García-Fuentes M, Collado MC, Sanz Y, EVASYON Study Group. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring)2009; 17(10): 1906-1915

[59] Nadal I, Santacruz A, Marcos A, Warnberg J, Garagorri JM, Moreno LA, Martin-Matillas M, Campoy C, Martí A, Moleres A, Delgado M, Veiga OL, García-Fuentes M, Redondo CG, Sanz Y. Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes (Lond)2009; 33(7): 758-767

[60] Wu X, Ma C, Han L, Nawaz M, Gao F, Zhang X, Yu P, Zhao C, Li L, Zhou A, Wang J, Moore JE, Millar BC, Xu J. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr Microbiol2010; 61(1): 69-78

[61] Larsen N, Vogensen FK, van den Berg FWJ, Nielsen DS, Andreasen AS, Pedersen BK, Al-Soud WA, Sørensen SJ, Hansen LH, Jakobsen M. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE2010; 5(2): e9085

[62] Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature2012; 490(7418): 55-60

[63] Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, Mariat D, Corthier G, Doré J, Henegar C, Rizkalla S, Clément K. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes2010; 59(12): 3049-3057

[64] Pictet RL, Rall LB, Phelps P, Rutter WJ. The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells. Science1976; 191(4223): 191-192

[65] Fontaine J, Le Douarin NM. Analysis of endoderm formation in the avian blastoderm by the use of quail-chick chimaeras. The problem of the neurectodermal origin of the cells of the APUD series. J Embryol Exp Morphol1977; 41(1): 209-222

[66] Sander M, German MS. The β cell transcription factors and development of the pancreas. J Mol Med (Berl)1997; 75(5): 327-340

[67] Edlund H. Transcribing pancreas. Diabetes1998; 47(12): 1817-1823

[68] St-Onge L, Wehr R, Gruss P. Pancreas development and diabetes. Curr Opin Genet Dev1999; 9(3): 295-300

[69] Wang S, Yan J, Anderson DA, Xu Y, Kanal MC, Cao Z, Wright CVE, Gu G. Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas. Dev Biol2010; 339(1): 26-37

[70] Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci USA2000; 97(4): 1607-1611

[71] Jensen J, Pedersen EE, Galante P, Hald J, Heller RS, Ishibashi M, Kageyama R, Guillemot F, Serup P, Madsen OD. Control of endodermal endocrine development by Hes-1. Nat Genet2000; 24(1): 36-44

[72] Schwitzgebel VM, Scheel DW, Conners JR, Kalamaras J, Lee JE, Anderson DJ, Sussel L, Johnson JD, German MS. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development2000; 127(16): 3533-3542

[73] Lee CS, Perreault N, Brestelli JE, Kaestner KH. Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity. Genes Dev2002; 16(12): 1488-1497

[74] Schonhoff SE, Giel-Moloney M, Leiter AB. Neurogenin 3-expressing progenitor cells in the gastrointestinal tract differentiate into both endocrine and non-endocrine cell types. Dev Biol2004; 270(2): 443-454

[75] Schonhoff SE, Giel-Moloney M, Leiter AB. Minireview: Development and differentiation of gut endocrine cells. Endocrinology2004; 145(6): 2639-2644

[76] Gu G, Dubauskaite J, Melton DA. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development2002; 129(10): 2447-2457

[77] Xu X, D’Hoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van de Casteele M, Mellitzer G, Ling Z, Pipeleers D, Bouwens L, Scharfmann R, Gradwohl G, Heimberg H. β cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell2008; 132(2): 197-207

[78] Kitamura T, Kitamura YI, Kobayashi M, Kikuchi O, Sasaki T, Depinho RA, Accili D. Regulation of pancreatic juxtaductal endocrine cell formation by FoxO1. Mol Cell Biol2009; 29(16): 4417-4430

[79] Lam EWF, Francis RE, Petkovic M. FOXO transcription factors: key regulators of cell fate. Biochem Soc Trans2006; 34( 5): 722-726

[80] Al-Masri M, Krishnamurthy M, Li J, Fellows GF, Dong HH, Goodyer CG, Wang R. Effect of forkhead box O1 (FOXO1) on beta cell development in the human fetal pancreas. Diabetologia2010; 53(4): 699-711

[81] Talchai C, Xuan S, Kitamura T, DePinho RA, Accili D. Generation of functional insulin-producing cells in the gut by Foxo1 ablation. Nat Genet2012; 44(4): 406-412

[82] Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature1999; 402(6762): 656-660

[83] Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology2000; 141(11): 4255-4261

[84] Schellekens H, Finger BC, Dinan TG, Cryan JF. Ghrelin signalling and obesity: at the interface of stress, mood and food reward. Pharmacol Ther2012; 135(3): 316-326

[85] Hosoda H, Kojima M, Matsuo H, Kangawa K. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun2000; 279(3): 909-913

[86] Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori K, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab2000; 85(12): 4908-4911

[87] Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol2001; 280(5): R1483-R1487

[88] Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab2002; 87(6): 2988

[89] Volante M, Allìa E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab2002; 87(3): 1300-1308

[90] 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 Metab2001; 86(10): 5083-5086

[91] Damjanovic SS, Lalic NM, Pesko PM, Petakov MS, Jotic A, Miljic D, Lalic KS, Lukic L, Djurovic M, Djukic VB. Acute effects of ghrelin on insulin secretion and glucose disposal rate in gastrectomized patients. J Clin Endocrinol Metab2006; 91(7): 2574-2581

[92] Rodieux F, Giusti V, D’Alessio DA, Suter M, Tappy L. Effects of gastric bypass and gastric banding on glucose kinetics and gut hormone release. Obesity (Silver Spring)2008; 16(2): 298-305

[93] Korner J, Inabnet W, Conwell IM, Taveras C, Daud A, Olivero-Rivera L, Restuccia NL, Bessler M. Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity (Silver Spring)2006; 14(9): 1553-1561

[94] Morínigo R, Casamitjana R, Moizé V, Lacy AM, Delgado S, Gomis R, Vidal J. Short-term effects of gastric bypass surgery on circulating ghrelin levels. Obes Res2004; 12(7): 1108-1116

[95] Leonetti F, Silecchia G, Iacobellis G, Ribaudo MC, Zappaterreno A, Tiberti C, Iannucci CV, Perrotta N, Bacci V, Basso MS, Basso N, Di Mario U. Different plasma ghrelin levels after laparoscopic gastric bypass and adjustable gastric banding in morbid obese subjects. J Clin Endocrinol Metab2003; 88(9): 4227-4231

[96] Lin E, Gletsu N, Fugate K, McClusky D, Gu LH, Zhu JL, Ramshaw BJ, Papanicolaou DA, Ziegler TR, Smith CD. The effects of gastric surgery on systemic ghrelin levels in the morbidly obese. Arch Surg2004; 139(7): 780-784

[97] Tritos NA, Mun E, Bertkau A, Grayson R, Maratos-Flier E, Goldfine A. Serum ghrelin levels in response to glucose load in obese subjects post-gastric bypass surgery. Obes Res2003; 11(8): 919-924

[98] le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lönroth H, Fändriks L, Ghatei MA, Bloom SR, Olbers T. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg2007; 246(5): 780-785

[99] Korner J, Bessler M, Cirilo LJ, Conwell IM, Daud A, Restuccia NL, Wardlaw SL. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab2005; 90(1): 359-365

[100] Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology2007; 132(6): 2131-2157

[101] Wren AM, Bloom SR. Gut hormones and appetite control. Gastroenterology2007; 132(6): 2116-2130

[102] Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature2006; 444(7121): 854-859

[103] Falkén Y, Hellström PM, Holst JJ, Näslund E. Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides. J Clin Endocrinol Metab2011; 96(7): 2227-2235

[104] Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet1987; 330(8571): 1300-1304

[105] Preitner F, Ibberson M, Franklin I, Binnert C, Pende M, Gjinovci A, Hansotia T, Drucker DJ, Wollheim C, Burcelin R, Thorens B. Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors. J Clin Invest2004; 113(4): 635-645

[106] Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest1967; 46(12): 1954-1962

[107] Laferrère B, Heshka S, Wang K, Khan Y, McGinty J, Teixeira J, Hart AB, Olivan B. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care2007; 30(7): 1709-1716

[108] Dirksen C, Hansen DL, Madsbad S, Hvolris LE, Naver LS, Holst JJ, Worm D. Postprandial diabetic glucose tolerance is normalized by gastric bypass feeding as opposed to gastric feeding and is associated with exaggerated GLP-1 secretion: a case report. Diabetes Care2010; 33(2): 375-377

[109] Borg CM, le Roux CW, Ghatei MA, Bloom SR, Patel AG, Aylwin SJB. Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety. Br J Surg2006; 93(2): 210-215

[110] de Carvalho CP, Marin DM, de Souza AL, Pareja JC, Chaim EA, de Barros Mazon S, da Silva CA, Geloneze B, Muscelli E, Alegre SM. GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism. Obes Surg2009; 19(3): 313-320

[111] Goldfine AB, Mun EC, Devine E, Bernier R, Baz-Hecht M, Jones DB, Schneider BE, Holst JJ, Patti ME. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Metab2007; 92(12): 4678-4685

[112] Holdstock C, Zethelius B, Sundbom M, Karlsson FA, Edén Engström B. Postprandial changes in gut regulatory peptides in gastric bypass patients. Int J Obes (Lond)2008; 32(11): 1640-1646

[113] Korner J, Bessler M, Inabnet W, Taveras C, Holst JJ. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis2007; 3(6): 597-601

[114] Laferrère B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, Lee H, Yapp K, Olivan B. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab2008; 93(7): 2479-2485

[115] le Roux CW, Aylwin SJB, Batterham RL, Borg CM, Coyle F, Prasad V, Shurey S, Ghatei MA, Patel AG, Bloom SR. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg2006; 243(1): 108-114

[116] Morínigo R, Moizé V, Musri M, Lacy AM, Navarro S, Marín JL, Delgado S, Casamitjana R, Vidal J. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab2006; 91(5): 1735-1740

[117] Cohen RV, Schiavon CA, Pinheiro JS, Correa JL, Rubino F. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m²: a report of 2 cases. Surg Obes Relat Dis2007; 3(2): 195-197

[118] 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. Gastroenterology1985; 89(5): 1070-1077

[119] Kervran A, Blache P, Bataille D. Distribution of oxyntomodulin and glucagon in the gastrointestinal tract and the plasma of the rat. Endocrinology1987; 121(2): 704-713

[120] 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 Metab1983; 57(3): 488-495

[121] Polak JM, Bloom S, Coulling I, Pearse AGE. Immunofluorescent localization of enteroglucagon cells in the gastrointestinal tract of the dog. Gut1971; 12(4): 311-318

[122] Laferrère B, Swerdlow N, Bawa B, Arias S, Bose M, Oliván B, Teixeira J, McGinty J, Rother KI. Rise of oxyntomodulin in response to oral glucose after gastric bypass surgery in patients with type 2 diabetes. J Clin Endocrinol Metab2010; 95(8): 4072-4076

[123] Holst JJ. Enteroglucagon. Annu Rev Physiol1997; 59(1): 257-271

[124] Cohen MA, Ellis SM, Le Roux CW, Batterham RL, Park A, Patterson M, Frost GS, Ghatei MA, Bloom SR. Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab2003; 88(10): 4696-4701

[125] 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. Diabetes2005; 54(8): 2390-2395

[126] Dakin CL, Gunn I, Small CJ, Edwards CMB, Hay DL, Smith DM, Ghatei MA, Bloom SR. Oxyntomodulin inhibits food intake in the rat. Endocrinology2001; 142(10): 4244-4250

[127] Parlevliet ET, Heijboer AC, Schröder-van der Elst JP, Havekes LM, Romijn JA, Pijl H, Corssmit EPM. Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet. Am J Physiol Endocrinol Metab2008; 294(1): E142-E147

[128] Maida A, Lovshin JA, Baggio LL, Drucker DJ. The glucagon-like peptide-1 receptor agonist oxyntomodulin enhances β-cell function but does not inhibit gastric emptying in mice. Endocrinology2008; 149(11): 5670-5678

[129] Kerr BD, Flatt PR, Gault VA. (D-Ser2)Oxm[mPEG-PAL]: a novel chemically modified analogue of oxyntomodulin with antihyperglycaemic, insulinotropic and anorexigenic actions. Biochem Pharmacol2010; 80(11): 1727-1735

[130] Lundberg JM, Tatemoto K, Terenius L, Hellström PM, Mutt V, Hökfelt T, Hamberger B. Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc Natl Acad Sci USA1982; 79(14): 4471-4475

[131] Böttcher G, Sjölund K, Ekblad E, Håkanson R, Schwartz TW, Sundler F. Coexistence of peptide YY and glicentin immunoreactivity in endocrine cells of the gut. Regul Pept1984; 8(4): 261-266

[132] Roth CL, Enriori PJ, Harz K, Woelfle J, Cowley MA, Reinehr T. Peptide YY is a regulator of energy homeostasis in obese children before and after weight loss. J Clin Endocrinol Metab2005; 90(12): 6386-6391

[133] Alvarez Bartolomé M, Borque M, Martinez-Sarmiento JM, Aparicio E, Hernández C, Cabrerizo L, Fernández-Represa JA. Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty. Obes Surg2002; 12(3): 324-327

[134] 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. Nature2002; 418(6898): 650-654

[135] Viardot A, Heilbronn LK, Herzog H, Gregersen S, Campbell LV. Abnormal postprandial PYY response in insulin sensitive nondiabetic subjects with a strong family history of type 2 diabetes. Int J Obes (Lond)2008; 32(6): 943-948

[136] Pittner RA, Moore CX, Bhavsar SP, Gedulin BR, Smith PA, Jodka CM, Parkes DG, Paterniti JR, Srivastava VP, Young AA. Effects of PYY[3-36] in rodent models of diabetes and obesity. Int J Obes Relat Metab Disord2004; 28(8): 963-971

[137] Boey D, Heilbronn L, Sainsbury A, Laybutt R, Kriketos A, Herzog H, Campbell LV. Low serum PYY is linked to insulin resistance in first-degree relatives of subjects with type 2 diabetes. Neuropeptides2006; 40(5): 317-324

[138] Berthoud HR, Shin AC, Zheng H. Obesity surgery and gut-brain communication. Physiol Behav2011; 105(1): 106-119

Acknowledgements

We thank Katsuhisa Horimoto for helpful discussions. This work was supported by grants from the National Basic Research Program of China (973 Program, 2011CB504003 to H.Z.), the National Natural Science Foundation of China (Grant No. 61134013 to H.Z., No. 81070657 to H.Z.), and NN-CAS Research Foundation (NNCAS-2009-1 to H.Z.).

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