Effect of Alrestatin Sodium on Glucose-Stimulated Insulin Secretion in the Fasted Anaesthetized Rat

Abstract

In the anaesthetized fasted non-diabetic male intact rat, alrestatin sodium injected as a bolus (0.75 mmol/kg, i.v.) did not affect basal plasma insulin or glucose levels. However, in response to an intravenous glucose tolerance test, plasma insulin levels were significantly increased above the values observed in the animal during a control test. The decreases in plasma glucose levels after alrestatin were significantly greater than in the control study. In rat pancreatic preparations in vitro, alrestatin lowered the basal release of ³H-norepinephrine and also the release obtained with the catecholamine-releasing agent tyramine. A modulation of catecholamine release appears to be of importance in the mode of action of alrestatin with respect to the insulin secretion and plasma glucose levels. It is suggested that alrestatin may play a useful role in the therapy of diabetes mellitus since it can augment insulin secretion when glucose is administered to a fasted animal in which the acute insulin response has been shown to be like that of the human diabetic, and in addition, can lower arginine-stimulated glucagon secretion in the animal, the latter being a model of an action that is observed in the human diabetic. The net effect of these hormonal changes has been predicted previously to be a lowering of the blood glucose levels in the human diabetic patient.

Key words

Alrestatin Sodium (AY-22,284-A) - Intravenous Glucose Tolerance Test - Plasma Glucose Level - Plasma Insulin Level - Norepinephrine Release in vitro Pancreatic Preparation - Diabetes - Anaesthetized Fasted Rat