Effects of cholecystokinin (CCK)-8, CCK-33, and gastric inhibitory polypeptide (GIP) on basal and meal-stimulated pancreatic hormone secretion in man.
Gastrointestinal hormones with insulinotropic effects, like cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) might tentatively be used in the treatment of non-insulin-dependent diabetes mellitus. We therefore examined the effects of intravenous injection of pharmacological dose levels of CCK-8 (100 and 300 pmol/kg), CCK-33 (100 pmol/kg), GIP (100 pmol/kg), and CCK-8 plus GIP (100 pmol/kg of each) on plasma levels of glucose, insulin, somatostatin, glucagon, and pancreatic polypeptide (PP) in healthy human volunteers. The peptides were given under basal conditions or in combination with a mixed meal. CCK-8, CCK-33, and GIP were all found to increase the basal plasma levels of insulin, somatostatin, and PP; the increases were observed already in samples taken at 2 min after the injection. In contrast, the plasma glucagon levels were unaffected by the peptides. CCK-8, CCK-33, and GIP (100 pmol/kg) all potentiated the meal-induced plasma responses of insulin and PP, whereas plasma levels of glucagon after the meal were not affected. Plasma somatostatin levels after the meal were increased by GIP but not affected by CCK-8 or CCK-33. CCK-8 and GIP together (100 pmol/kg for both) increased plasma levels of insulin, PP and somatostatin as much as each of the peptides given alone, both under basal conditions and after the meal intake. Plasma levels of glucagon were not affected by CCK-8 and GIP together. We conclude that in man, both CCK-8, CCK-33, and GIP moderately stimulate basal and meal related insulin release without any synergistic effects and that the peptides do not inhibit the secretion of glucagon.
Ahrén
B
B
Department of Pharmacology, Lund University, Sweden.
Pettersson
M
M
Uvnäs-Moberg
K
K
Gutniak
M
M
Efendic
S
S
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D004435:Eating / Q000502:physiology*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D010187:Pancreatic Hormones / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000097:blood / Q000378:metabolism; D012016:Reference Values; D012844:Sincalide / Q000494:pharmacology*; D013004:Somatostatin / Q000097:blood / Q000378:metabolism; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D010187:Pancreatic Hormones; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide; D005934:Glucagon; D002766:Cholecystokinin; D012844:Sincalide