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

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Abstract
The effect of priming normal subjects with glucose or with Arg on subsequent insulin and glucagon responses was investigated. A 60 min glucose infusion markedly enhanced the insulin response to a 2nd glucose infusion, initiated 60 min after the end of the 1st one. When the insulin release caused by the 1st glucose infusion was blocked by somatostatin, enhancement of the response to the 2nd infusion was still present. The action of glucose in inducing a time-dependent potentiation in the islet is not secondary to events associated with granular exocytosis. Arg infused over 30 min, failed to enhance either the insulin or the glucagon response to a 2nd Arg infusion given 60 or 90 min later. When glucose was given as a rapid i.v. injection, it inhibited the insulin response to a 2nd glucose load 30 min later. This effect of glucose was independent of its acute stimulation of insulin release: addition of somatostatin to the 1st glucose injection abolished the acute insulin response, but not the inhibition of the 2nd response. Priming with Arg, either given as an infusion or as a rapid i.v. injection, caused the inhibition of the subsequent insulin responses to Arg. In the case of priming with a 30-min Arg infusion, this inhibitory effect could be detected 60 and 90 min later. When priming was through rapid i.v. bolus, inhibition of the 2nd 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 Arg did not modify the subsequent inhibition of the insulin response. Glucose-induced time-dependent inhibition and potentiation of subsequent insulin release is not generated by the insulin secretion process per se. Arg does not generate time-dependent potentiation of insulin or glucagon release. Arg 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. 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.