CHARACTERIZATION OF INSULIN SECRETION AFTER CONTINUOUS EXPOSURE OF NORMAL ISOLATED PERFUSED RAT PANCREAS FOR MORE THAN SIX HOURS TO GLUCOSE, THEOPHYLLINE AND TOLBUTAMIDE

A perfusion system was conducted for more than 6 hours in response to glucose (16.7mM), theophylline (5 mM ) and tolbutamide (100 µg/ml) to give an insight about the B-cell secretory capacity. Continuous exposure of the isolated pancreas to glucose (16.7 mM ) caused a biphasic response. After 3 h of continuous glucose perfusion a significant sustained reduction in the insulin secretion rates to about 22% of the maximal response untill 6 h was observed .Then, after 15 min with 3 mM glucose perfusion, re-infusion of glucose 16.7 mM produced an increase in insulin secretion .Theophylline infusion for 6 h did not significanly affect the insulin secretion induced by re-infusion of theophylline after 15 min with low glucose ( 3 mM) concentration. The results also indicated that even after exposure of the pancreas to glucose 16.7 mM for 6 h, theophylline was able to restore the stimulatory effect after desensitization. Continuous exposure of the pancreas for long time (6 h) to tolbutamide significanly inhibit its ability to secrete insulin after 15 min of basal perfusion medium which demonstrated a desensitization phenomenon. The results revealed that, B-cells become desensitized, not exhausted, not only by glucose but also with tolbutamide. It seems also that CAMP system cann't be neglected in this model since, theophylline induced insulin secretion alone and even after long infusion with high glucose. The desensitization of the B-cell to tolbutamide may be due to sustained depolarization caused by continuous exposure to tolbutamide . The present study confirms that the elevation of plasma glucose concentration represents a pathogenic factor which causes a deleterious effect on islet B-cell function. This effect is reversed on cessation of glucose.