Effects of insulin and acarbose alone and in combination in the female streptozotocin-induced diabetic rat

Abstract

Diabetes is characterized by hyperphagia, polydipsia, polyuria, elevations in blood and urinary glucose, and alterations in the adrenergic nervous system. Insulin treatment is effective in reversing most of the adverse conditions of diabetes in the streptozotocin-treated rat. Acarbose (BAY G 5421), an intestinal α-glucosidase inhibitor, decreases postprandial glycemia by delaying carbohydrate absorption and also affords some beneficial effects in the diabetic animal. The purpose of this study was to evaluate the effects of chronic insulin (⩽2 U/day) with and without acarbose treatment (20 mg/100 g of diet) on the metabolic and adrenergic parameters altered in streptozotocin (50 mg/kg, intravenously)-induced diabetes in female rats. Insulin dosage was changed weekly after the first 2 weeks of treatment in both insulin-treated groups in an attempt to maintain a level of blood glucose that was comparable to that achieved with acarbose treatment alone. Insulin dosage was reduced to a greater extent in the dual-treated group than in the group treated with insulin alone. Diabetic rats were hyperphagic, polydipsic, and polyuric within 1 week of streptozotocin treatment. Each treatment alone was effective in reducing these alterations. However, these reductions were more apparent in the combined therapy group. Only in this combined therapy group was glycated hemoglobin returned to normal. All treatments also prevented the significant weight loss observed in untreated diabetic animals. Adrenergic responses were assessed by monitoring the rise in tail skin temperature associated with administration of isoproterenol. Diabetic rats were less responsive than controls, and each of the treatments restored this response. Terminal blood sampling revealed that T₄ but not T₃ was significantly reduced in the diabetic group and T₄ was restored to control values with both single and combined treatments. Collectively, these data suggest that combined insulin and acarbose therapy has a much greater beneficial effect than does individual therapy alone and that the insulin requirement can be reduced with adjunctive acarbose treatment.