Insulin treatment improves glucose-induced insulin release in rats with NIDDM induced by streptozocin

Insulin-deficient diabetes in humans, as well as in the neonatal streptozocin-induced rat model of non-insulin-dependent diabetes mellitus (NIDDM), are associated with islet beta-cell insensitivity to glucose. We hypothesized that the chronic hyperglycemia-hypoinsulinemia pattern causes this impairment of the glucose influence on insulin secretion. This study was designed to determine whether the glucose defect could be counteracted by normalizing the diabetic state in rats with NIDDM after insulin therapy. Mixte lente insulin (5 U X kg-1 X day-1) was given daily at 1700 h over 24 h or 5 consecutive days. Insulin secretion was studied the morning after the last insulin injection with the isolated perfused pancreas preparation. Fed basal plasma glucose levels decreased in diabetic rats from 183 +/- 8 to 136 +/- 10 mg/dl after the 1-day insulin treatment and to 135 +/- 5 mg/dl after the 5-day insulin treatment (vs. 116 +/- 3 mg/dl in control rats). Pancreatic insulin stores were not affected by insulin therapy. Although the 1-day insulin treatment did not modify the lack of glucose response in the diabetic rats, the 5-day insulin treatment improved their glucose-induced insulin secretion. Moreover, insulin therapy improved the priming effect of glucose on a second stimulation with glucose. The return of this glucose effect was hardly detectable after the 1-day insulin therapy but was clearly present after the 5-day treatment.(ABSTRACT TRUNCATED AT 250 WORDS)