Abstract
Bariatric surgery is the most effective modality of achieving weight loss as well as the most effective treatment for type 2 diabetes mellitus (T2DM). Glucose-dependent insulinotropic polypeptide (GIP) is an incretin and is implicated in the pathogenesis of obesity and T2DM. Its role in weight loss and resolution of T2DM after bariatric surgery is very controversial. We have made an attempt to review the physiology of GIP and its role in weight loss and resolution of T2DM after bariatric surgery. We searched PubMed and included all relevant original articles (both human and animal) in the review. Whereas most human studies have shown a decrease in GIP post-malabsorptive bariatric surgery, the role of GIP in bariatric surgery done in animal experiments remains inconclusive.
Similar content being viewed by others
References
McIntosh CH, Widenmaier S, Kim SJ. Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide; GIP). Vitam Horm. 2009;80:409–71.
Lu M, Wheeler MB, Leng XH, et al. The role of the free cytosolic calcium level in beta-cell signal transduction by gastric inhibitory polypeptide and glucagon-like peptide I (7–37). Endocrinology. 1993;132:94–100.
Siegel EG, Creutzfeldt W. Stimulation of insulin release in isolated rat islets by GIP in physiological concentrations and its relation to islet cyclic AMP content. Diabetologia. 1985;28:857–61.
Ross SA, Dupre J. Effects of ingestion of triglyceride or galactose on secretion of gastric inhibitory polypeptide and on responses to intravenous glucose in normal and diabetic subjects. Diabetes. 1978;27:327–33.
Ehses JA, Casilla VR, Doty T, et al. Glucose-dependent insulinotropic polypeptide promotes beta-(INS-1) cell survival via cyclic adenosine monophosphate-mediated caspase-3 inhibition and regulation of p38 mitogen-activated protein kinase. Endocrinology. 2003;144:4433–45.
Kim SJ, Winter K, Nian C, et al. Glucose-dependent insulinotropic polypeptide (GIP) stimulation of pancreatic beta-cell survival is dependent upon phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling, inactivation of the forkhead transcription factor Foxo1, and down-regulation of bax expression. J Biol Chem. 2005;280:22297–307.
Kim SJ, Nian C, Widenmaier S, et al. Glucose-dependent insulinotropic polypeptide-mediated up-regulation of beta-cell antiapoptotic Bcl-2 gene expression is coordinated by cyclic AMP (cAMP) response element binding protein (CREB) and cAMP-responsive CREB coactivator 2. Mol Cell Biol. 2008;28:1644–56.
Creutzfeldt W. The entero-insular axis in type 2 diabetes—incretins as therapeutic agents. Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S288–303.
Cheeseman CI, O’Neill D. Basolateral D-glucose transport activity along the crypt–villus axis in rat jejunum and upregulation induced by gastric inhibitory peptide and glucagon-like peptide-2. Exp Physiol. 1998;83:605–16.
Cheeseman CI, Tsang R. The effect of GIP and glucagon-like peptides on intestinal basolateral membrane hexose transport. Am J Physiol. 1996;271:G477–82.
Girard J. The incretins: from the concept to their use in the treatment of type 2 diabetes. Part A: incretins: concept and physiological functions. Diabetes Metab. 2008;34:550–9.
Oben J, Morgan L, Fletcher J, et al. Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7–36) amide, on fatty acid synthesis in explants of rat adipose tissue. J Endocrinol. 1991;130:267–72.
Hauner H, Glatting G, Kaminska D, et al. Effects of gastric inhibitory polypeptide on glucose and lipid metabolism of isolated rat adipocytes. Ann Nutr Metab. 1988;32:282–88.
Yamada C, Yamada Y, Tsukiyama K, et al. The murine glucagon-like peptide-1 receptor is essential for control of bone resorption. Endocrinology. 2008;149:574–79.
Tsukiyama K, Yamada Y, Yamada C, et al. Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Mol Endocrinol. 2006;20:1644–51.
Meier JJ, Nauck MA, Schmidt WE, et al. Gastric inhibitory polypeptide: the neglected incretin revisited. Regul Pept. 2002;107:1–13.
Vilsboll T, Agerso H, Lauritsen T, et al. The elimination rates of intact GIP as well as its primary metabolite, GIP 3–42, are similar in type 2 diabetic patients and healthy subjects. Regul Pept. 2006;137:168–72.
Hupe-Sodmann K, McGregor GP, Bridenbaugh R, et al. Characterisation of the processing by human neutral endopeptidase 24.11 of GLP-1(7–36) amide and comparison of the substrate specificity of the enzyme for other glucagon-like peptides. Regul Pept. 1995;58:149–56.
Elahi D, Andersen DK, Muller DC, et al. The enteric enhancement of glucose-stimulated insulin release. The role of GIP in aging, obesity, and non-insulin-dependent diabetes mellitus. Diabetes. 1984;33:950–57.
Vilsboll T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003;88:2706–13.
Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002;8:738–42.
Theodorakis MJ, Carlson O, Muller DC, et al. Elevated plasma glucose-dependent insulinotropic polypeptide associates with hyperinsulinemia in impaired glucose tolerance. Diabetes Care. 2004;27:1692–8.
Knop FK, Vilsboll T, Hojberg PV, et al. The insulinotropic effect of GIP is impaired in patients with chronic pancreatitis and secondary diabetes mellitus as compared to patients with chronic pancreatitis and normal glucose tolerance. Regul Pept. 2007;144:123–30.
Lynn FC, Pamir N, Ng EH, et al. Defective glucose-dependent insulinotropic polypeptide receptor expression in diabetic fatty Zucker rats. Diabetes. 2001;50:1004–11.
Piteau S, Olver A, Kim SJ, et al. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat. Biochem Biophys Res Commun. 2007;362:1007–12.
Knop FK, Vilsboll T, Hojberg PV, et al. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state. Diabetes. 2007;56:1951–9.
Meier JJ, Hucking K, Holst JJ, et al. Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes. 2001;50:2497–504.
Vilsboll T, Krarup T, Madsbad S, et al. Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients. Diabetologia. 2002;45:1111–9.
Pilgaard K, Jensen CB, Schou JH, et al. The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia. 2009;52:1298–307.
Gniuli D, Calcagno A, Dalla LL, et al. High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats. Diabetologia. 2010;53:2233–40.
Rijkelijkhuizen JM, McQuarrie K, Girman CJ, et al. Effects of meal size and composition on incretin, alpha-cell, and beta-cell responses. Metabolism. 2010;59:502–11.
Rudnicki M, Patel DG, McFadden DW, et al. Proximal jejunal and biliary effects on the enteroinsular axis. Surgery. 1990;107:455–60.
Rubino F. Is type 2 diabetes an operable intestinal disease? A provocative yet reasonable hypothesis. Diabetes Care. 2008;31 Suppl 2:S290–6.
de Campos Martins MV, Peixoto AA, Schanaider A, et al. Glucose tolerance in the proximal versus the distal small bowel in Wistar rats. Obes Surg. 2009;19:202–6.
Little TJ, Doran S, Meyer JH, et al. The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed. Am J Physiol Endocrinol Metab. 2006;291:E647–55.
Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244:741–9.
Cote GA, Edmundowicz SA. Emerging technology: endoluminal treatment of obesity. Gastrointest Endosc. 2009;70:991–9.
Wang TT, Hu SY, Gao HD, et al. Ileal transposition controls diabetes as well as modified duodenal jejunal bypass with better lipid lowering in a nonobese rat model of type II diabetes by increasing GLP-1. Ann Surg. 2008;247:968–75.
Pories WJ, Albrecht RJ. Etiology of type II diabetes mellitus: role of the foregut. World J Surg. 2001;25:527–31.
Santoro S. Is the metabolic syndrome a disease of the foregut? Yes, excessive foregut. Ann Surg. 2008;247:1074–5.
Kindel TL, Yoder SM, D’Alessio DA, et al. The effect of duodenal-jejunal bypass on glucose-dependent insulinotropic polypeptide secretion in Wistar rats. Obes Surg. 2010;20:768–75.
Strader AD, Vahl TP, Jandacek RJ, et al. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab. 2005;288:E447–53.
Rubino F, Marescaux J. Effect of duodenal–jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;239:1–11.
Pacheco D, de Luis DA, Romero A, et al. The effects of duodenal–jejunal exclusion on hormonal regulation of glucose metabolism in Goto–Kakizaki rats. Am J Surg. 2007;194:221–4.
McClean PL, Irwin N, Hunter K, et al. (Pro(3))GIP[mPEG]: novel, long-acting, mPEGylated antagonist of gastric inhibitory polypeptide for obesity-diabetes (diabesity) therapy. Br J Pharmacol. 2008;155:690–701.
Flatt PR. Dorothy Hodgkin Lecture 2008. Gastric inhibitory polypeptide (GIP) revisited: a new therapeutic target for obesity-diabetes? Diabet Med. 2008;25:759–64.
Whitson BA, Leslie DB, Kellogg TA, et al. Entero-endocrine changes after gastric bypass in diabetic and nondiabetic patients: a preliminary study. J Surg Res. 2007;141:31–9.
Korner J, Bessler M, Inabnet W, et al. 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 Dis. 2007;3:597–601.
Rubino F, Gagner M, Gentileschi P, et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240:236–42.
Clements RH, Gonzalez QH, Long CI, et al. Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg. 2004;70:1–4.
Laferrere B, Teixeira J, McGinty J, et al. 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 Metab. 2008;93:2479–85.
Laferrere B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care. 2007;30:1709–16.
Guidone C, Manco M, Valera-Mora E, et al. Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes. 2006;55:2025–31.
Mingrone G, Nolfe G, Gissey GC, et al. Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion. Diabetologia. 2009;52:873–81.
Salinari S, Bertuzzi A, Asnaghi S, et al. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care. 2009;32:375–80.
Shak JR, Roper J, Perez-Perez GI, et al. The effect of laparoscopic gastric banding surgery on plasma levels of appetite-control, insulinotropic, and digestive hormones. Obes Surg. 2008;18:1089–96.
DePaula AL, Macedo AL, Schraibman V, et al. Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20–34. Surg Endosc. 2009;23:1724–32.
Cohen RV, Schiavon CA, Pinheiro JS, et al. 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 Dis. 2007;3:195–7.
Lee HC, Kim MK, Kwon HS, et al. Early changes in incretin secretion after laparoscopic duodenal–jejunal bypass surgery in type 2 diabetic patients. Obes Surg. 2010;20:1530–5.
Naslund E, Backman L, Holst JJ, et al. Importance of small bowel peptides for the improved glucose metabolism 20 years after jejunoileal bypass for obesity. Obes Surg. 1998;8:253–60.
Ockander L, Hedenbro JL, Rehfeld JF, et al. Jejunoileal bypass changes the duodenal cholecystokinin and somatostatin cell density. Obes Surg. 2003;13:584–90.
Guldstrand M, Ahren B, Naslund E, et al. Dissociated incretin response to oral glucose at 1 year after restrictive vs. malabsorptive bariatric surgery. Diabetes Obes Metab. 2009;11:1027–33.
Peterli R, Wolnerhanssen B, Peters T, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250:234–41.
Deacon CF, Nauck MA, Meier J, et al. Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab. 2000;85:3575–81.
Nauck MA, Heimesaat MM, Behle K, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab. 2002;87:1239–46.
Imeryuz N, Yegen BC, Bozkurt A, et al. Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol. 1997;273:G920–27.
Sancho V, Trigo MV, Martin-Duce A, et al. Effect of GLP-1 on D-glucose transport, lipolysis and lipogenesis in adipocytes of obese subjects. Int J Mol Med. 2006;17:1133–37.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rao, R.S., Kini, S. GIP and Bariatric Surgery. OBES SURG 21, 244–252 (2011). https://doi.org/10.1007/s11695-010-0305-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11695-010-0305-x