Hormonal responses during development of streptozotocin diabetes in rats

The pancreatic B-cytolytic agent streptozotocin (STZ) was administered at high and low doses to male Sprague-Dawley rats at the time of weaning (20-30 d). During the next 15 weeks growth, food intake, glycemia and circulating insulin (IRI), glucagon (IRG) and corticosterone (CS) levels were measured at regular intervals. Within seven days after receiving the highest dose of STZ the rats exhibited a severe and persistent diabetes characterized by depressed growth, elevated food intake, insulinopenia and increased concentrations of IRG and CS. With lower doses, a slowly developing hyperglycemia was observed which after a delay of 4 to 6 weeks equalled in severity that of the high dose group. There were also corresponding delays in the appearance of the other major symptoms of the diabetes. Glucose tolerance tests performed 6 weeks after STZ showed that both high and low dose groups were severely glucose intolerant and neither group exhibited an IRI response to glucose challenge. Multiple regression analyses of the hormone levels of individual rats during the developing diabetes revealed that hyperglucagonemia and hyperglycemia arose simultaneously, while insulinopenia was delayed in appearance and only correlated significantly to glycemia late in the experiment. These data suggest that streptozotocin diabetes initially arises from increased glucagon production coupled with a limited capacity of the pancreas to secrete insulin in response to hyperglycemia. Subsequently, the contribution of other factors including continued B-cytolysis, insulinopenia, and elevated adrenal cortical hormones results in the development of the full diabetic syndrome.