EFFECTS OF CHRONIC GLIPIZIDE TREATMENT ON THE NIDD HEART

Extrapancreatic activity of the sulfonylurea, glipizide, was evaluated in the neonatal streptozotocin-induced rat model of noninsulin-dependent diabetes. Two day old Wistar rats were given a bolus of streptozotocin (90 mg/kg i.p.) to cause noninsulin-dependent diabetes; these animals became severely glucose intolerant and eventually developed a cardiomyopathy characterized by reduced heart rate, contractility and cardiac output. Male littermates injected with citrate buffer served as nondiabetic controls. At four weeks of age, the nondiabetic and NIDD rats were administered by gavage either glipizide (2.5 mg/kg) or the methyl cellulose vehicle. Throughout the treatment protocol, no difference in the degree of glucose intolerance was observed between the glipizide-treated and vehicle-treated animals. Glipizide therapy also was ineffective in improving plasma insulin levels, which were significantly depressed in the diabetic group. Yet, animals treated with glipizide for one year exhibited improved myocardial contractile function relative to the vehicle-fed or ad lib fed diabetic animals. Heart rate was significantly elevated and there was a tendency for both the rate of relaxation and contractility to be elevated in sulfonylurea-treated group. Glipizide also reduced the degree of insulin resistance in the heart. Since these changes occur in the absence of changes in glucose tolerance or insulin levels, the heart appears to be very sensitive to the direct effects of the sulfonylureas.