Effects of glucagon like peptide-1 to mediate glycemic effects of weight loss surgery

Abstract

To date, weight loss surgeries are the most effective treatment for obesity and glycemic control in patients with type 2 diabetes. Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG), two widely used bariatric procedures for the treatment of obesity, induce diabetes remission independent of weight loss while glucose improvement after adjustable gastric banding (AGB) is proportional to the amount of weight loss. The immediate, weight-loss independent glycemic effect of gastric bypass has been attributed to postprandial hyperinsulinemia and an enhanced incretin effect. The rapid passage of nutrients into the intestine likely accounts for significantly enhanced glucagon like-peptide 1 (GLP-1) secretion, and postprandial hyperinsulinemia after GB is typically attributed to the combined effects of elevated glucose and GLP-1. For this review we focus on the beneficial effects of the three most commonly performed bariatric procedures, RYGB, SG, and AGB, on glucose metabolism and diabetes remission. Central to this discussion will be the extent to which the effects of surgery are mediated by GLP-1. Better understanding of these mechanisms could provide insight to development of novel therapeutic strategies for treatment of diabetes as well as refinement of surgical techniques.

Mucosal glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide cell numbers in the super-obese human foregut after gastric bypass

“…The present data on increased density of GLP-1-producing L-cells are in line with a body of evidence showing increased circulating GLP-1 levels [28,29]. A stronger effect on GLP-1 cell density was evident in BP200 compared with BP60, suggesting that the length of the BP-limb plays a role.…”

Untitled

“…In these cases, many patients are discharged without the need to continue using oral hypoglycemic agents. The main reason is the increase in GLP-1, which promotes insulinotropic effects in the pancreas [134]. Another factor that contributes greatly to the enhancement of this intestinal hormone after bariatric surgery is the change in dietary patterns, in most patients, with a higher percentage of fatty foods consumed, which stimulate the secretion of GLP-1 by L cells [135] .…”

Untitled

“…Evidence also suggests that the fact of promoting higher and more stable concentrations of GLP-1 produces an important improvement in B cell function, as well as an overall increase in B cell mass [60], while these observations have not been confirmed in humans, the hyperinsulinemic hypoglycemia syndrome following gastric bypass has been suggested as a period of hyperactivity/ hyperplasia of B cells due to GLP-1, and that can be reverted with the use of exendin (9-39) [61][62][63]. Nevertheless, there is evidence which yields the past statements controversial [64].…”