TY - JOUR

T1 - Cholecystokinin secretion is suppressed by glucagon-like peptide-1

T2 - clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs

AU - Rehfeld, Jens F.

AU - Knop, Filip K.

AU - Asmar, Ali

AU - Madsbad, Sten

AU - Holst, Jens J.

AU - Asmar, Meena

PY - 2018

Y1 - 2018

N2 - Objective: Recent randomized and controlled trials of drugs derived from the gut hormone glucagon-like peptide-1 (GLP-1) show that the most frequent adverse symptoms are gastrointestinal, including gallbladder-related side effects such as cholithiasis and cholecystitis. Since the gut hormone cholecystokinin (CCK) stimulates bile secretion and regulates gallbladder motility and emptying, we examined the effect of GLP-1 on the secretion of CCK in normal subjects and patients with type 1 diabetes mellitus. Materials and methods: Plasma was sampled from 10 healthy subjects and 10 patients with diabetes. With plasma glucose concentrations clamped between 6 and 9 nmol/l, GLP-1 or saline was infused for 240 min during and after a meal. The plasma concentrations of CCK were measured with a highly specific radioimmunoassay. Results: Basal plasma concentrations of CCK were similar in the normal subjects and in the diabetes patients. During the meal, the CCK concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of CCK significantly in both normal subjects and in the diabetes patients. Conclusions: The results show that GLP-1 suppresses the secretion of CCK after a meal in normal and diabetic subjects. The suppression attenuates the gallbladder contractility. Our data, therefore, offer an explanation for the increased risk of adverse gallbladder events during treatment with GLP-1-derived drugs.

AB - Objective: Recent randomized and controlled trials of drugs derived from the gut hormone glucagon-like peptide-1 (GLP-1) show that the most frequent adverse symptoms are gastrointestinal, including gallbladder-related side effects such as cholithiasis and cholecystitis. Since the gut hormone cholecystokinin (CCK) stimulates bile secretion and regulates gallbladder motility and emptying, we examined the effect of GLP-1 on the secretion of CCK in normal subjects and patients with type 1 diabetes mellitus. Materials and methods: Plasma was sampled from 10 healthy subjects and 10 patients with diabetes. With plasma glucose concentrations clamped between 6 and 9 nmol/l, GLP-1 or saline was infused for 240 min during and after a meal. The plasma concentrations of CCK were measured with a highly specific radioimmunoassay. Results: Basal plasma concentrations of CCK were similar in the normal subjects and in the diabetes patients. During the meal, the CCK concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of CCK significantly in both normal subjects and in the diabetes patients. Conclusions: The results show that GLP-1 suppresses the secretion of CCK after a meal in normal and diabetic subjects. The suppression attenuates the gallbladder contractility. Our data, therefore, offer an explanation for the increased risk of adverse gallbladder events during treatment with GLP-1-derived drugs.

KW - Cholecystokinin

KW - cholecystitis

KW - cholelithiasis

KW - diabetes mellitus

KW - glucagon-like peptide 1

KW - side effects

U2 - 10.1080/00365521.2018.1530297

DO - 10.1080/00365521.2018.1530297

M3 - Journal article

C2 - 30449207

VL - 53

SP - 1429

EP - 1432

JO - Scandinavian Journal of Gastroenterology. Supplement

JF - Scandinavian Journal of Gastroenterology. Supplement

SN - 0085-5928

IS - 12

ER -