title: Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. dpsonne@gmail.com
authors.forename: David P
authors.initials: DP
authors.lastname: Sonne
authors.forename: Kristine J
authors.initials: KJ
authors.lastname: Hare
authors.forename: Pernille
authors.initials: P
authors.lastname: Martens
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002763:Cholecystectomy; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005768:Gastrointestinal Hormones / Q000097:blood*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D053767:Glucagon-Like Peptide 2 / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D002096:C-Peptide; D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon