Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans.
OBJECTIVE
Acute hyperglycemia inhibits gallbladder contraction. In non-diabetic subjects this inhibitory effect may result from endogenous hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin-stimulated gallbladder motility.


METHODS
Gallbladder volume (ultrasonography) and duodenal bilirubin output were studied simultaneously in nine healthy volunteers (age 20-52 years) on 3 separate occasions in random order during: (a) saline infusion (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mmol/l), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/l, glucose at 4-5 mmol/l). After a 2-h basal clamp period, cholecystokinin was infused intravenously for 60 min at 0.25 IDU x kg(-1) x h(-1), followed by another 60 min at 0.5 IDU x kg(-1) x h(-1).


RESULTS
HI and HG significantly (p<0.05) reduced basal duodenal bilirubin output compared to control, while basal gallbladder volume did not change. At the low dose cholecystokinin, gallbladder emptying during HG (25+/-3%) and HI (39+/-4%) was significantly (p<0.01) reduced compared to control (61+/-4%). The inhibitory effect of HG was significantly (p<0.05) stronger compared to HI. Duodenal bilirubin output during the low dose cholecystokinin was significantly (p<0.05) reduced by HG, but not by HI. No inhibitory effect of HG and HI on gallbladder emptying and duodenal bilirubin output was observed with the high dose of cholecystokinin.


CONCLUSIONS
In healthy subjects acute hyperglycemia and euglycemic hyperinsulinemia reduce basal duodenal bilirubin output and inhibit gallbladder emptying stimulated by low dose cholecystokinin. These results suggest that insulin is involved in the inhibitory effect of hyperglycemia on basal and cholecystokinin-stimulated gallbladder motility.
Gielkens
H A
HA
Department of Gastroenterology-Hepatology, Leiden University Medical Center, The Netherlands.
Lam
W F
WF
Coenraad
M
M
Frölich
M
M
van Oostayen
J A
JA
Lamers
C B
CB
Masclee
A A
AA
D000328:Adult; D000704:Analysis of Variance; D001481:Basal Metabolism; D001786:Blood Glucose / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D005260:Female; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D016473:Gallbladder Emptying / Q000187:drug effects; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D006946:Hyperinsulinism / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D013268:Stimulation, Chemical
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D002766:Cholecystokinin