TY - JOUR

T1 - Mechanisms of surgical control of type 2 diabetes

T2 - GLP-1 is key factor

AU - Holst, Jens Juul

AU - Madsbad, Sten

N1 - Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

PY - 2016/7

Y1 - 2016/7

N2 - GLP-1 secretion in response to meals is dramatically increased after gastric bypass operations. GLP-1 is a powerful insulinotropic and anorectic hormone, and analogs of GLP-1 are widely used for the treatment of diabetes and recently approved also for obesity treatment. It is, therefore, reasonable to assume that the exaggerated GLP-1 secretion contributes to the antidiabetic and anorectic effects of gastric bypass. Indeed, human experiments with the GLP-1 receptor antagonist, Exendin 9-39, have shown that the improved insulin secretion, which is responsible for part of the antidiabetic effect of the operation, is reduced and or abolished after GLP-1 receptor blockade. Also the postoperative improvement of glucose tolerance is eliminated and or reduced by the antagonist, pointing to a key role for the exaggerated GLP-1 secretion. Indeed, there is evidence that the exaggerated GLP-1 secretion is also responsible for postprandial hypoglycemia sometimes observed after bypass. Other operations (biliopancreatic-diversion and or sleeve gastrectomy) appear to involve different and/or additional mechanisms, and so does experimental bariatric surgery in rodents. However, unlike bypass surgery in humans, the rodent operations are generally associated with increased energy metabolism pointing to an entirely different mechanism of action in the animals.

AB - GLP-1 secretion in response to meals is dramatically increased after gastric bypass operations. GLP-1 is a powerful insulinotropic and anorectic hormone, and analogs of GLP-1 are widely used for the treatment of diabetes and recently approved also for obesity treatment. It is, therefore, reasonable to assume that the exaggerated GLP-1 secretion contributes to the antidiabetic and anorectic effects of gastric bypass. Indeed, human experiments with the GLP-1 receptor antagonist, Exendin 9-39, have shown that the improved insulin secretion, which is responsible for part of the antidiabetic effect of the operation, is reduced and or abolished after GLP-1 receptor blockade. Also the postoperative improvement of glucose tolerance is eliminated and or reduced by the antagonist, pointing to a key role for the exaggerated GLP-1 secretion. Indeed, there is evidence that the exaggerated GLP-1 secretion is also responsible for postprandial hypoglycemia sometimes observed after bypass. Other operations (biliopancreatic-diversion and or sleeve gastrectomy) appear to involve different and/or additional mechanisms, and so does experimental bariatric surgery in rodents. However, unlike bypass surgery in humans, the rodent operations are generally associated with increased energy metabolism pointing to an entirely different mechanism of action in the animals.

KW - Journal Article

KW - Review

U2 - 10.1016/j.soard.2016.02.033

DO - 10.1016/j.soard.2016.02.033

M3 - Journal article

C2 - 27313194

VL - 12

SP - 1236

EP - 1242

JO - Surgery for Obesity and Related Diseases

JF - Surgery for Obesity and Related Diseases

SN - 1550-7289

IS - 6

ER -