Sonne, David P3; Hare, Kristine J3; Martens, Pernille3; Rehfeld, Jens F6; Holst, Jens Juul7; Vilsbøll, Tina6; Knop, Filip K6
1 Section of Endocrinology Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Section for Translational Metabolic Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet6 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet7 Section for Translational Metabolic Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet
Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.
American Journal of Physiology: Gastrointestinal and Liver Physiology, 2013, Vol 304, Issue 4
Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Adult; Aged; Bile Acids and Salts; Blood Glucose; C-Peptide; Cholecystectomy; Female; Gastric Emptying; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Insulin; Male; Middle Aged; Postprandial Period