Effect of cholecystokinin-A receptor blockade on postprandial insulinaemia and gastric emptying in humans.
Our aim was determine the relationship between cholecystokinin (CCK)-A receptor blockade, glucose levels, insulin secretion and gastric emptying in humans, and to assess the effect of CCK-A blockade on pancreatic polypeptide secretion. After a 12-h fast, six healthy volunteers were given [99mTc]iminodiacetic acid monosodium salt (IDA) intravenously (5 mCi). One hour later they were offered a 577 kcal liquid meal containing [99mTc]diethylenetriaminepentaacetic acid (DTPA) (2 mCi) and glucose (105 g). Scintigraphic gastric and gallbladder activity, and plasma glucose, insulin and pancreatic polypeptide responses were monitored. In a second experiment, a continuous intravenous infusion of loxiglumide (7.5 mg kg h(-1)) was started 60 min before and continued until 120 min after test meal ingestion to block the CCK-A receptors. Gallbladder emptying was blocked by loxiglumide. Loxiglumide accelerated gastric emptying, increased insulin secretion without alteration of glucose profiles, and abolished all phases of the postprandial pancreatic polypeptide response. Blockade of peripheral CCK-A receptors accelerates gastric emptying of liquids with an increase in postprandial insulin levels. The lack of changes in glycaemia suggests that alternative homeostatic mechanisms also control postprandial glucose levels. Inhibition of pancreatic polypeptide release may reflect an independent effect of loxiglumide on vagal control involved in pancreatic polypeptide release.
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018709:Statistics, Nonparametric
D001786:Blood Glucose; D007328:Insulin; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D011377:Proglumide