Exaggerated Glucagon-Like Peptide 1 Response Is Important for Improved β-Cell Function and Glucose Tolerance After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes

β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)–specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

• Publication year

  2013

• Venue

  Diabetes

• Publication date

  2013-08-15

• Fields of study

  Medicine

• Identifiers
  DOI 10.2337/db13-0022PMID 23649520PMCID 3749359
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy

  2013cited by this paper
• Banting Memorial Lecture 2012 Reversing the twin cycles of Type 2 diabetes

  2013influential reference
• Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux‐en‐Y gastric bypass

  2013cited by this paper
• Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass

  2012influential reference
• Bariatric surgery versus conventional medical therapy for type 2 diabetes.

  2012cited by this paper
• Very-low-calorie diet: a quick therapeutic tool to improve β cell function in morbidly obese patients with type 2 diabetes.

  2012cited by this paper
• The Role of Endogenous Incretin Secretion as Amplifier of Glucose-Stimulated Insulin Secretion in Healthy Subjects and Patients With Type 2 Diabetes

  2012cited by this paper
• Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects

  2012influential reference
• Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance.

  2012influential reference
• [Bariatric surgery versus conventional medical therapy for type 2 diabetes].

  2012cited by this paper
• The effect of a very low calorie diet on insulin sensitivity, beta cell function, insulin clearance, incretin hormone secretion, androgen levels and body composition in obese young women

  2012cited by this paper
• Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol

  2011cited by this paper
• Early Improvement in Glycemic Control After Bariatric Surgery and Its Relationships with Insulin, GLP-1, and Glucagon Secretion in Type 2 Diabetic Patients

  2011cited by this paper
• Endogenous GLP-1 regulates postprandial glycemia in humans: relative contributions of insulin, glucagon, and gastric emptying.

  2011influential reference
• Hepatic and Peripheral Insulin Sensitivity and Diabetes Remission at 1 Month After Roux-en-Y Gastric Bypass Surgery in Patients Randomized to Omentectomy

  2011cited by this paper
• Roux-en-Y gastric bypass corrects hyperinsulinemia implications for the remission of type 2 diabetes.

  2011cited by this paper
• Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1–Stimulated Postprandial Insulin Secretion in Humans

  2011cited by this paper
• 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.

  2011cited by this paper
• Antidiabetic Actions of Endogenous and Exogenous GLP-1 in Type 1 Diabetic Patients With and Without Residual β-Cell Function

  2011influential reference
• Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes

  2011cited by this paper
• The role of beta-cell function and insulin sensitivity in the remission of type 2 diabetes after gastric bypass surgery.

  2011cited by this paper
• Improvement in ß-cell function in patients with normal and hyperglycemia following Roux-en-Y gastric bypass surgery.

  2010cited by this paper
• Effect of Endogenous GLP-1 on Insulin Secretion in Type 2 Diabetes

  2010cited by this paper
• The Importance of Caloric Restriction in the Early Improvements in Insulin Sensitivity After Roux-en-Y Gastric Bypass Surgery

  2010influential reference
• Acute effects of gastric bypass versus gastric restrictive surgery on β-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes

  2010cited by this paper
• Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

  2009cited by this paper
• Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes.

  2008cited by this paper
• The physiology of glucagon-like peptide 1.

  2007influential reference
• GLP-1 and Changes in Glucose Tolerance following Gastric Bypass Surgery in Morbidly Obese Subjects

  2006cited by this paper
• Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes.

  2005cited by this paper
• Effect of Laparoscopic Roux-En Y Gastric Bypass on Type 2 Diabetes Mellitus

  2003cited by this paper
• Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs.

  2002cited by this paper
• The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction

  2001cited by this paper
• Assessment of hepatic insulin action in obese type 2 diabetic patients.

  2001cited by this paper
• Ilial Transposition and Enteroglucagon/GLP-1 in Obesity (and Diabetic?) Surgery

  1999cited by this paper
• Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39.

  1999cited by this paper
• Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans.

  1998cited by this paper
• Exendin-(9-39) Is an Inverse Agonist of the Murine Glucagon-Like Peptide-1 Receptor: Implications for Basal Intracellular Cyclic Adenosine 3',5'-Monophosphate Levels and β-Cell Glucose Competence* *This work was supported by Grant 31-46958.96 from the Swiss National Science Foundation (to B.T.).

  1998cited by this paper
• Importance of Small Bowel Peptides for the Improved Glucose Metabolism 20 Years after Jejunoileal Bypass for Obesity

  1998cited by this paper
• Exendin-(9-39) is an inverse agonist of the murine glucagon-like peptide-1 receptor: implications for basal intracellular cyclic adenosine 3',5'-monophosphate levels and beta-cell glucose competence.

  1998cited by this paper
• Role of Glucose Effectiveness in the Determination of Glucose Tolerance

  1996cited by this paper
• ISEC: a program to calculate insulin secretion.

  1996cited by this paper
• Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult‐Onset Diabetes Mellitus

  1995cited by this paper
• Tissue and Plasma Concentrations of Amidated and Glycine-Extended Glucagon-Like Peptide I in Humans

  1994cited by this paper
• Quantification of the Relationship Between Insulin Sensitivity and β-Cell Function in Human Subjects: Evidence for a Hyperbolic Function

  1993cited by this paper
• Cloning and Functional Expression of the Human Islet GLP-1 Receptor: Demonstration That Exendin-4 Is an Agonist and Exendin-(9–39) an Antagonist of the Receptor

  1993cited by this paper
• Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance

  1992cited by this paper
• Dose-Response Relationship Between Lymph Insulin and Glucose Uptake Reveals Enhanced Insulin Sensitivity of Peripheral Tissues

  1992cited by this paper
• Exendin-3, a novel peptide from Heloderma horridum venom, interacts with vasoactive intestinal peptide receptors and a newly described receptor on dispersed acini from guinea pig pancreas. Description of exendin-3(9-39) amide, a specific exendin receptor antagonist.

  1991cited by this paper
• Insulin transport across capillaries is rate limiting for insulin action in dogs.

  1989cited by this paper
• Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus.

  1985cited by this paper
• The heterogeneity of gastric inhibitory polypeptide in porcine and human gastrointestinal mucosa evaluated with five different antisera.

  1984cited by this paper
• Diminished immunoreactive gastric inhibitory polypeptide response to a meal in newly diagnosed type I (insulin-dependent) diabetics.

  1983cited by this paper

• Efficacy and safety of single-anastomosis gastric bypass variants versus sleeve gastrectomy or Roux-en-Y gastric bypass: a systematic review and meta-analysis.

  2026cites this paper
• The (dys)regulation of energy storage in obesity.

  2025cites this paper
• Hormonal Alterations in Individuals with Obesity After Metabolic Bariatric Surgery: A Narrative Review

  2025cites this paper
• β-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes.

  2025cites this paper
• Mechanism of Diabetes Remission or Improvement in Glucose Control Following Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Systematic Review and Meta-Analysis

  2025cites this paper
• Acute effects of GIP and GLP‐1 receptor antagonism in totally pancreatectomized individuals: A randomized double‐blind, placebo‐controlled crossover study

  2025cites this paper
• SADI-S and SG surgeries induce distinct bile acid profiles linked to improved glucose metabolism via microbiota interactions

  2025cites this paper
• Duodenal enteroendocrine cells and GIP as treatment targets for obesity and type 2 diabetes.

  2024cites this paper
• HbA1c Reductions Following Sleeve Gastrectomy Versus Sleeve Gastrectomy With Proximal Jejunal Bypass: Significant Differences in Diabetic Patients

  2024cites this paper
• Insights into the Neurobiology of Weight Loss after Bariatric Surgery and GLP-1R Agonists.

  2024cites this paper
• GLP-1 and IL-6 regulates obesity in the gut and brain.

  2024cites this paper
• Vagal activation alters prandial bile acid composition and glycemia in patients with hypoglycemia after Roux‐en‐Y gastric bypass surgery

  2024cites this paper
• New Lessons from the gut: studies of the role of gut peptides in weight loss and diabetes resolution after gastric bypass and sleeve gastrectomy.

  2024cites this paper
• Differential effect of endogenous glucagon‐like peptide‐1 on prandial glucose counterregulatory response to hypoglycaemia in humans with and without bariatric surgery

  2024cites this paper
• Does GLP-1 cause post-bariatric hypoglycemia: 'Computer says no'

  2024cites this paper
• Effect of ghrelin on glucose tolerance, gut hormones, appetite, and food intake after sleeve gastrectomy.

  2024cites this paper
• The role of glucagon-like peptide 1 in the postprandial effects of metformin in type 2 diabetes: a randomized crossover trial.

  2024cites this paper
• GLP‐1 enhances β‐cell response to protein ingestion and bariatric surgery amplifies it

  2024cites this paper
• Gut peptides before and following Roux‐En‐Y gastric bypass: A systematic review and meta‐analysis

  2024cites this paper
• Mechanism of metabolic surgery for the treatment of Type 2 Diabetes Mellitus (T2DM)

  2023cites this paper
• Insulinoma After Bariatric Surgery: Tricks for Diagnosis and Therapeutic Approach

  2023cites this paper
• Individuals with type 2 diabetes have higher density of small intestinal neurotensin-expressing cells

  2023cites this paper
• Bariatric Surgery: Targeting pancreatic β cells to treat type II diabetes

  2023cites this paper
• βHB inhibits glucose-induced GLP-1 secretion in GLUTag and human jejunal enteroids.

  2023cites this paper
• Gut microbiome modified by bariatric surgery improves insulin sensitivity and correlates with increased brown fat activity and energy expenditure

  2023cites this paper
• Effects of bariatric surgery and dietary intervention on insulin resistance and appetite hormones over a 3 year period

  2023cites this paper
• Pre-Meal Whey Protein Alters Postprandial Insulinemia by Enhancing β-Cell Function and Reducing Insulin Clearance in T2D

  2023cites this paper
• Contribution of endogenous glucagon-like peptide 1 to prandial counterregulatory responses to hypoglycemia after bariatric surgery

  2023cites this paper
• Increased Insulin Secretion and Glucose Effectiveness in Obese Patients with Type 2 Diabetes following Bariatric Surgery

  2023cites this paper
• Annals of Clinical and Medical Case Reports

  2023cites this paper
• The oral disposition index calculated from a meal tolerance test is a crucial indicator for evaluating differential normalization of postprandial glucose and triglyceride excursions in morbidly obese patients after laparoscopic sleeve gastrectomy.

  2023cites this paper
• A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass

  2023cites this paper
• Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals with Obesity and Pre-Diabetes.

  2023cites this paper
• Differential effects of RYGB surgery and best medical treatment for obesity-diabetes on intestinal and islet adaptations in obese-diabetic ZDSD rats

  2022cites this paper
• Interorgan crosstalk in pancreatic islet function and pathology

  2022cites this paper
• Targeting the Enteroendocrine System for Treatment of Obesity.

  2022cites this paper
• Vertical sleeve gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice

  2022cites this paper
• N‐terminal alterations turn the gut hormone GLP‐2 into an antagonist with gradual loss of GLP‐2 receptor selectivity towards more GLP‐1 receptor interaction

  2022cites this paper
• Beneficial effects of SGLT2 inhibitor on metabolic inflexibility and visceral fat amount in animal model of obese type 2 diabetes

  2022cites this paper
• The importance of endogenously secreted GLP-1 and GIP for postprandial glucose tolerance and β-cell function after Roux-en-Y gastric bypass and sleeve gastrectomy surgery.

  2022cites this paper
• Glucagon‐like peptide‐1 effect on β‐cell function varies according to diabetes remission status after Roux‐en‐Y gastric bypass

  2022influential citation
• Association between hemoglobin A1C response to glucagon-like peptide-1 receptor agonists and hemoglobin A1C and weight outcomes post-bariatric surgery

  2022cites this paper
• Plasma GDF15 levels are similar between subjects after bariatric surgery and matched controls and are unaffected by meals.

  2021cites this paper
• Model-Based Assessment of C-Peptide Secretion and Kinetics in Post Gastric Bypass Individuals Experiencing Postprandial Hyperinsulinemic Hypoglycemia

  2021cites this paper
• Which predictors could effect on remission of type 2 diabetes mellitus after the metabolic surgery: A general perspective of current studies?

  2021cites this paper
• A pilot study about the development and characterization of a Roux en Y gastric bypass model in obese Yucatan minipigs

  2021cites this paper
• The role of bariatric surgery in the management of nonalcoholic steatohepatitis

  2021cites this paper
• Exendin(9‐39)NH2: Recommendations for clinical use based on a systematic literature review

  2021cites this paper
• Gastrointestinal Peptides in Eating-Related Disorders.

  2021cites this paper
• Microbial regulation of enteroendocrine cells.

  2021cites this paper
• What Is an L-Cell and How Do We Study the Secretory Mechanisms of the L-Cell?

  2021cites this paper
• GLP-1: 10-year follow-up after Roux-en-Y gastric bypass

  2021cites this paper
• The role of GLP-1 in postprandial glucose metabolism after bariatric surgery: a narrative review of human GLP-1 receptor antagonist studies.

  2021cites this paper
• Factors Affecting Metabolic Outcomes Post Bariatric Surgery: Role of Adipose Tissue

  2021cites this paper
• Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

  2021influential citation
• Revisional Surgeries of Laparoscopic Sleeve Gastrectomy

  2021cites this paper
• Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion

  2021cites this paper
• FXR‐mediated epigenetic regulation of GLP‐1R expression contributes to enhanced incretin effect in diabetes after RYGB

  2021cites this paper
• The Role of Incretins on Insulin Function and Glucose Homeostasis

  2021cites this paper
• The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes.

  2021cites this paper
• DMSO_A_295162 575..588

  2021cites this paper
• Intravital imaging of islet Ca2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice

  2021cites this paper
• Important Role of the GLP-1 Axis for Glucose Homeostasis after Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery Bariatric Surgery you.

  2021influential citation
• Effects of bariatric surgery on cardiorespiratory fitness: A systematic review and meta‐analysis

  2021cites this paper
• Metabolic Messengers: glucagon-like peptide 1

  2021cites this paper
• Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass

  2021cites this paper
• Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission.

  2021cites this paper
• Gastrointestinal hormones and β-cell function after gastric bypass and sleeve gastrectomy: an RCT (Oseberg).

  2021cites this paper
• Alterations in the Liver Fat Fraction Features Examined by Magnetic Resonance Imaging Following Bariatric Surgery: a Self-Controlled Observational Study

  2020cites this paper
• From Entero-Endocrine Cell Biology to Surgical Interventional Therapies for Type 2 Diabetes.

  2020cites this paper
• Responses of gut and pancreatic hormones, bile acids and fibroblast growth factor-21 differ to glucose, protein and fat ingestion after gastric bypass surgery.

  2020cites this paper
• CCK‐1 and CCK‐2 receptor agonism do not stimulate GLP‐1 and neurotensin secretion in the isolated perfused rat small intestine or GLP‐1 and PYY secretion in the rat colon

  2020cites this paper
• GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals.

  2020cites this paper
• Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery

  2020cites this paper
• Simulating the Post-gastric Bypass Intestinal Microenvironment Uncovers a Barrier-Stabilizing Role for FXR

  2020cites this paper
• Incretins in obesity and diabetes

  2020cites this paper
• Bariatric Surgery and Type 1 Diabetes: Unanswered Questions

  2020cites this paper
• Cerebral effects of glucagon‐like peptide‐1 receptor blockade before and after Roux‐en‐Y gastric bypass surgery in obese women: A proof‐of‐concept resting‐state functional MRI study

  2020cites this paper
• The Perfect Sleeve Gastrectomy: A Clinical Guide to Evaluation, Treatment, and Techniques

  2020cites this paper
• How the Sleeve Gastrectomy Works: Metabolically

  2020cites this paper
• Intestinal Hormones

  2020cites this paper
• Bariatric surgery normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice

  2020cites this paper
• Enteroendocrine Hormone Secretion and Metabolic Control: Importance of the Region of the Gut Stimulation

  2020cites this paper
• The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery.

  2020cites this paper
• Gut Mucosal Gene Expression and Metabolic Changes After Roux‐en‐Y Gastric Bypass Surgery

  2020cites this paper
• GK-rats respond to gastric bypass surgery with improved glycemia despite unaffected insulin secretion and beta cell mass.

  2020cites this paper
• Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery: 1-year prospective study

  2020cites this paper
• Glucagon-Like Peptide-1: Actions and Influence on Pancreatic Hormone Function.

  2020cites this paper
• Obesity, adipose tissue, and bariatric surgery.

  2020cites this paper
• Is bariatric surgery resolving NAFLD via microbiota-mediated bile acid ratio reversal? A comprehensive review.

  2020cites this paper
• Intravital imaging of islet Ca2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice

  2020cites this paper
• Separate and Combined Glucometabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1 in Healthy Individuals

  2019cites this paper
• Mechanisms of action of a carbohydrate-reduced, high-protein diet in reducing the risk of postprandial hypoglycemia after Roux-en-Y gastric bypass surgery.

  2019cites this paper
• Contribution of endogenous glucagon-like peptide-1 to changes in glucose metabolism and islet function in people with type 2 diabetes four weeks after Roux-en-Y gastric bypass (RYGB).

  2019cites this paper
• PYY plays a key role in the resolution of diabetes following bariatric surgery in humans

  2019cites this paper
• Editorial: What's New in Endocrinology?

  2019cites this paper
• Bariatric Surgery in the Treatment of Type 2 Diabetes

  2019cites this paper
• Gut Peptide Agonism in the Treatment of Obesity and Diabetes.

  2019cites this paper
• Comparison of Diabetes Remission and Micronutrient Deficiency in a Mildly Obese Diabetic Rat Model Undergoing SADI-S Versus RYGB

  2019cites this paper
• Intestinal sensing and handling of dietary lipids in gastric bypass-operated patients and matched controls.

  2019cites this paper