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-depend ent diabetes. Two day old Wistar rats were given a bolus of streptozot ocin (90 mg/kg i.p.) to cause noninsulin-dependent diabetes; these ani mals became severely glucose intolerant and eventually developed a car diomyopathy characterized by reduced heart rate, contractility and car diac output. Male littermates injected with citrate buffer served as n ondiabetic controls. At four weeks of age, the nondiabetic and NIDD ra ts were administered by gavage either glipizide (2.5 mg/kg) or the met hyl cellulose vehicle. Throughout the treatment protocol, no differenc e in the degree of glucose intolerance was observed between the glipiz ide-treated and vehicle-treated animals. Glipizide therapy also was in effective 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 relati ve to the vehicle-fed or ad lib fed diabetic animals. Heart rate was s ignificantly elevated and there was a tendency for both the rate of re laxation and contractility to be elevated in sulfonylurea-treated grou p. Glipizide also reduced the degree of insulin resistance in the hear t. Since these changes occur in the absence of changes in glucose tole rance or insulin levels, the heart appears to be very sensitive to the direct effects of the sulfonylureas.