Mechanisms of surgical control of type 2 diabetes: GLP-1 is key factor.
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.
NNF Center for Basic Metabolic Research and Department of Biomedical Research, the Panum Institute, Copenhagen, Denmark. Electronic address: jjholst@sund.ku.dk.
Jens Juul
JJ
Holst
Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
Sten
S
Madsbad
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000601:surgery*; D004195:Disease Models, Animal; D015390:Gastric Bypass / Q000379:methods*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D053767:Glucagon-Like Peptide 2 / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007408:Intestinal Absorption / Q000502:physiology; D051379:Mice; D009765:Obesity / Q000601:surgery; D010446:Peptide Fragments / Q000494:pharmacology; D012074:Remission Induction
D001647:Bile Acids and Salts; D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D007328:Insulin; D010446:Peptide Fragments; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1
Exendin 9-39; GLP-1receptor antagonists; Glucagon-like peptide-1; PYY; Peptide YY; RYGB; Reactive hypoglycemia; Roux-en-Y gastric bypass