Proglumide antagonizes cholecystokinin effects on plasma glucose and insulin in rats in vivo

Abstract

Proglumide was shown to possess a low affinity for cholecystokinin (CCK) receptors and to inhibit the synergistic action of CCK 8 on glucose-mediated insulin release in vitro. Proglumide (400 mg/kg i.p., given 15 min before an i.v. combination of CCK 8 and glucose) reversed the CCK 8 (0.5 nmol/kg)-induced increase of plasma insulin levels and decrease of glucose levels. It had no effect on plasma insulin and glucose levels when the glucose bolus was administered alone. Camostate (400 mg/kg p.o.; Foy-305; a trypsin inhibitor acting via endogenously released CCK) increased plasma insulin levels by 10 μU/ml during an oral glucose (500 mg/kg) tolerance test. Pretreatment with proglumide (400 mg/kg i.p.) antagonized this effect. The data indicate that proglumide has an antagonistic effect on either exogenously added or endogenously released CCK with respect to plasma insulin and glucose levels and that it has no effect on plasma insulin and glucose levels when glucose is given alone. Therefore, proglumide and the newly developed, more potent CCK receptor antagonists are able to disturb insulin and glucose homoeostasis.