Effects of cholecystokinin, secretin, and pancreatic polypeptide on secretion of gastric inhibitory polypeptide, insulin, and glucagon

Abstract

Although the capacity of food components to cause more insulin secretion when given orally than when given intravenously is related significantly to increased plasma concentration of gastric inhibitory polypeptide (GIP), stimulated only by the oral route, questions arise as to what extent other gastrointestinal hormones modify insulin secretion either directly or by influencing the secretion of GIP. The triacontatriapeptide form of cholecystokinin (CCK 33), infused in dose gradients intravenously in dogs increases insulin secretion, and comparably to equimolar doses of the carboxy-terminal octapeptide of cholecystokin (CCK 8); neither compound changes fasting plasma levels of GIP or glucose. Glucagon was increased only by the largest dose of CCK 8 (0.27 ug/kg). Unlike the situation with GIP, it is not necessary to increase the plasma glucose above fasting level to obtain the insulin-releasing action of CCK. When glucose is infused intravenously (2 g in 0.5 min) at the beginning of a 15-minute infusion of CCK 8 (10 ng/kg/min), the amount of insulin release is greater than is produced by CCK 8 or glucose alone. In the same type of experiment, the infusion of GIP, in equimolar amounts as CCK 8, plus glucose causes no more insulin secretion than is stimulated by glucose alone. Secretin has only a small stimulating action on insulin release, and pancreatic polypeptide (PP) has no effect. Neither secretin nor PP affects GIP secretion, whether either is given alone, or together, or with CCK 8. Either secretin or CCK 8 inhibits oral glucose-stimulated increase in plasma GIP. These inhibitory effects are probably very much related to the hormone-induced decrease in gastric emptying, but changes in somatostatin secretion and other hormones possibly exert contributory actions. In conclusion, GIP in certain dose ranges has been reported to cause major increase in insulin secretion, but we showed that the insulin-releasing action of a small dose of glucose (2 g) infused intravenously was not augmented by GIP (44.5 ng/kg/min), although it was significantly increased by an equimolar dose of CCK 8. When plasma glucose was maintained at a fasting level, gradient equimolar dosages of CCK 8 and CCK 33 had comparable insulin-releasing action; GIP had no effect.