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 β-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 · kg−1 · 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. The hyperresponse to arginine, characteristic of the untreated diabetic rat, returned similar to that in controls after a 1-day insulin therapy, and it was again amplified at high glucose levels, although amplification remained lower than that of control rats. This indicates that the potentiating effect of glucose on the response to arginine was regained more precociously than the acute insulin response to glucose after insulin therapy. These data agree with the hypothesis that the chronic hyperglycemia-hypoinsulinemia in the NIDDM rat causes abnormal glucose influence on glucose- and arginine-stimulated insulin release.

This content is only available via PDF.