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

Jørgensen, Nils B.; Dirksen, Carsten; Bojsen‐Møller, Kirstine N.; Jacobsen, Siv H.; Worm, Dorte; Hansen, Dorte L.; Kristiansen, Viggo B.; Navér, Lars; Madsbad, Sten; Holst, Jens J.

doi:10.2337/db13-0022

Cited by 273 publications

(264 citation statements)

References 55 publications

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“…65 Postprandial GLP-1 secretion is substantially and durably increased early after RYGB, before significant weight loss has occurred, due to increased delivery of nutrients to the distal small intestine. 127 The importance of the incretin effect is unclear, with some studies showing that GLP-1 receptor blockade abolishes the RYGB-related improvement in beta-cell glucose sensitivity and insulin secretion 127 while another study found only minimal impairment in glucose tolerance following GLP-1 blockade after RYGB. 128 The durability of the effect of bariatric surgery on glycaemic control has been observed in the Swedish Obese Subjects Study; 72% of individuals with T2D achieved remission two years after surgery and 36% had maintained T2D remission 10 years after surgery.…”

Section: Bariatric Surgerymentioning

confidence: 99%

Targeting beta-cell preservation in the management of type 2 diabetes

2017

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Type 2 diabetes (T2D) is widely considered a chronic and progressive disease without cure. As beta-cell function progressively declines over time, blood glucose rises. Current management of T2D involves incremental introduction of dietary and drug therapies to achieve normoglycaemia. However, recent studies have demonstrated remission of T2D following bariatric surgery, very low calorie diet or intensive insulin therapy, raising the possibility that the declining beta-cell function in T2D may be arrested or even reversed. The point at which such interventions are introduced in the course of T2D is key for clinical benefit. Future treatment strategies should be revised to target early betacell preservation and thus disease remission. This article reviews the pathogenesis of beta-cell dysfunction and evidence for the clinical benefit of preserving beta-cell function in T2D, and discusses the evidence for beta-cell preservation of current glucose-lowering therapies with particular reference to their effect when initiated at the time of diagnosis of T2D. Br J Diabetes 2017;17:134-144

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Section: Bariatric Surgerymentioning

confidence: 99%

Targeting beta-cell preservation in the management of type 2 diabetes

2017

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“…Exaggerated secretion of GLP-1 resulting in enhanced insulin secretion appears to be one of the important mechanisms underlying the resolution of diabetes often seen after gastric bypass surgery, as illustrated in experiments involving the GLP1R antagonist exendin 9-39, which eliminates the effect of the operation on insulin secretion and impairs glucose tolerance (77). The power of this mechanism is also illustrated by cases of reactive hypoglycemia after the operation, which may also be prevented by the antagonist (78), or by feeding through gastrostomy catheter, which eliminates the exaggerated GLP-1 response (79); the latter is in keeping with the principle that hypoglycemia results from extremely rapid carbohydrate entry into the small intestine (39).…”

Section: Gut Endocrine Regulation Of Glucose Metabolismmentioning

confidence: 99%

Roles of the Gut in Glucose Homeostasis

et al. 2016

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The gastrointestinal tract plays a major role in the regulation of postprandial glucose profiles. Gastric emptying is a highly regulated process, which normally ensures a limited and fairly constant delivery of nutrients and glucose to the proximal gut. The subsequent digestion and absorption of nutrients are associated with the release of a set of hormones that feeds back to regulate subsequent gastric emptying and regulates the release of insulin, resulting in downregulation of hepatic glucose production and deposition of glucose in insulin-sensitive tissues. These remarkable mechanisms normally keep postprandial glucose excursions low, regardless of the load of glucose ingested. When the regulation of emptying is perturbed (e.g., pyloroplasty, gastric sleeve or gastric bypass operation), postprandial glycemia may reach high levels, sometimes followed by profound hypoglycemia. This article discusses the underlying mechanisms.

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“…To identify the role of endogenous GLP-1 in the amelioration of impaired β-cell function after RYGBP, the specific GLP-1 receptor antagonist exendin 9-39 has been used in four cross sectional [48][49][50][51] studies and one short-term longitudinal 52 study in post-RYGBP patients. Exendin 9-39 completely blunts the recovery of β-cell glucose sensitivity (BCGS) 1 week and 3 months after RYGBP, 52 and worsens post-prandial glucose tolerance, although only minimally. 49 Exendin 9-39 suppresses insulin secretion in response to a meal by 50% 49,50 and corrects the profound reactive hypoglycemia in patients with severe neuroglycopenia.…”

Section: Antagonism Of Glp-1 Prevents the Improvement In β-Cell Functmentioning

confidence: 99%

Bariatric surgery and obesity: influence on the incretins

Laferrère

2016

Int J Obes Supp

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The gut hormone incretins have an important physiological role in meal-related insulin release and post-prandial glucose control. In addition to weight loss, the incretin hormones have a role in glucose control after bariatric surgery. The release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced after gastric bypass (RYGBP). The rapid transit of food from the gastric pouch to the distal ileum is responsible for the greater GLP-1 release after RYGBP. The incretin effect on insulin secretion, or the greater insulin response to oral glucose compared to an isoglycemic intravenous glucose challenge, is severely impaired in patients with type 2 diabetes, but is recovered rapidly after RYGBP. The improvement in insulin secretion rate and β-cell sensitivity to oral glucose after RYGBP is mediated by endogenous GLP-1, and is abolished by exendin 9-39, a specific GLP-1 receptor antagonist. While calorie restriction and weight loss have major effects on the rapid and sustained improvement of fasted glucose metabolism, the enhanced incretin effect is a key player in post-prandial glucose control after RYGBP.

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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

Cited by 273 publications

References 55 publications

Targeting beta-cell preservation in the management of type 2 diabetes

Targeting beta-cell preservation in the management of type 2 diabetes

Roles of the Gut in Glucose Homeostasis

Bariatric surgery and obesity: influence on the incretins

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