POTENTIATION AND INHIBITION OF INSULIN RELEASE IN MAN FOLLOWING PRIMING WITH GLUCOSE AND WITH ARGININE – EFFECT OF SOMATOSTATIN

Abstract

ABSTRACT The effect of priming normal subjects with glucose or with arginine on subsequent insulin and glucagon responses was investigated. A 60 min glucose infusion enhanced markedly the insulin response to a second glucose infusion, initiated 60 min after the end of the first one. When the insulin release caused by the first glucose infusion was blocked by somatostatin, enhancement of the response to the second infusion was still present. These results suggest that the action of glucose in inducing a time-dependent potentiation in the islet is not secondary to events associated with granular exocytosis. Arginine, infused over 30 min, failed to enhance either the insulin or the glucagon response to a second arginine infusion given 60 or 90 min later. When glucose was given as a rapid iv injection, it inhibited the insulin response to a second glucose load 30 min later. This effect of glucose was independent of its acute stimulation of insulin release: addition of somatostatin to the first glucose injection abolished the acute insulin response, but not the inhibition of the second response. Priming with arginine, either given as an infusion or as a rapid iv injection, caused the inhibition of the subsequent insulin responses to arginine. In the case of priming with a 30-min arginine infusion, this inhibitory effect could be detected 60 and 90 min later. When priming was through rapid iv bolus, inhibition of the second insulin response appeared after 10 and 20 min, but faded out at 40–60 min. No such inhibition of the consecutive glucagon responses was observed. As for glucose, addition of somatostatin to the priming injection of arginine did not modify the subsequent inhibition of the insulin response. The following is concluded: 1. Glucose-induced time-dependent inhibition and potentiation of subsequent insulin release is not generated by the insulin secretion process per se. 2. Arginine does not generate time-dependent potentiation of insulin or glucagon release. 3. Arginine generates time-dependent inhibition of subsequent insulin but not of glucagon release. In analogy to glucose this effect is not mediated by the insulin release per se. 4. The mechanisms of acute initiation of insulin release, of time-dependent potentiation and of time-dependent inhibition are different; somatostatin acts exclusively on the acute initiation.