Synergistic impact of cholecystokinin and gastric inhibitory polypeptide on the regulation of insulin secretion.
The modulation of insulin output from isolated perifused rat islets by the intestinal peptides cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) was assessed. In the presence of 7 mmol/L (126 mg/dL) glucose, but not 2.75 mmol/L (50 mg/dL) glucose, CCK (5 nmol/L) or GIP (50 ng/mL) alone evoke small insulin secretory responses. However, the combination of GIP (50 ng/mL) plus CCK (5 nmol/L) together with 7 mmol/L glucose results in a markedly amplified insulin secretory response. CCK (50 nmol/L) alone increases phosphoinositide (PI) hydrolysis in islets, an event reflected by an increase in 3H efflux from myo[2-3H]inositol prelabeled islets and parallel accumulations of labeled inositol phosphates. GIP (50 ng/mL) alone has no effect on PI hydrolysis. However, GIP reduces the quantitative impact of CCK on PI turnover, an effect attributable to the capacity of GIP to elevate islet cAMP levels. CCK has no significant effect on islet cAMP levels. The results support the concept that the synergistic action of these peptides on insulin output is mediated by their ability to generate separate beta cell second messenger molecules. Nutrient-regulated intestinal release of various peptides represents a remarkable control system to ensure the release of insulin from the beta cell in amounts commensurate with both the quantity and quality of nutrient intake.
Zawalich
W S
WS
Yale University School of Nursing, New Haven, CT 06536-0740.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D020109:Devazepide; D004347:Drug Interactions; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D001570:Benzodiazepinones; D007295:Inositol Phosphates; D007328:Insulin; D005576:Colforsin; D005749:Gastric Inhibitory Polypeptide; D002766:Cholecystokinin; D000242:Cyclic AMP; D020109:Devazepide