Comparison of beta-cell function after long-term treatment with either insulin, insulin plus gliclazide or gliclazide in neonatal streptozotocin-induced non-insulin-dependent diabetic rats.

There are no definite guidelines in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) as to whether the treatment of choice is insulin, a sulfonylurea or a combination of insulin and sulfonylurea. We have therefore tried to evaluate the long-term effects of these treatments on beta-cell function in a rat model of NIDDM. NIDDM rats were prepared by the injection of streptozotocin (60 mg, i.p.) on the 5th day after birth. At 10 weeks, an oral glucose tolerance test (2 g/kg) was performed and rats were divided into 4 groups, each of which had the same mean glucose tolerance. The treatment of each group with either NPH insulin (4 U/kg/day), or oral gliclazide (10 mg/kg/day by a stomach cannula), or a combination of the above two, or a control (vehicle for gliclazide) was started from 12 weeks of age and continued for 6 months. Rats were fed ad libitum with standard rat chow. The weight gain of diabetic rats treated with gliclazide alone and of the vehicle-treated diabetic rats during 6 months was less than that of the other groups receiving insulin. The fasting plasma glucose of the insulin-only treated group stayed at the initial level for 6 months, but that of the other groups increased gradually. The frequency of deterioration of glucose tolerance for oral glucose loading (2 g/kg) in the insulin-only treated group was smaller than that in the other diabetic groups at 3 at 6 months after the start of treatment. The increase in plasma IRI after the oral glucose loading of the insulin-only treated group was the largest among the 4 groups at 6 months. In the pancreas perfusion experiment, the insulin response to glucose in the insulin-only treated group was more preserved than that in the other groups of diabetic rats after 6 months of treatment. These results suggest that treatment with insulin is effective in preserving beta-cell function in a rat model of NIDDM, whereas treatment with a sulfonylurea agent is not only ineffective but might negate the protective effect of insulin because the insulin-plus-gliclazide treated group elicited results similar to those of the gliclazide-only treated group except for the weight gain.