STREPTOZOTOCIN-INDUCED DIABETES-MELLITUS IN CYNOMOLGUS MONKEYS - CHANGES IN CARBOHYDRATE-METABOLISM, SKIN GLYCATION, AND PANCREATIC-ISLETS

Chronic hyperglycemia has been implicated in a number of diabetes mell itus-related conditions in the human population, including retinopathy , neuropathy, nephropathy, and vasculopathy, However, it has beets dif ficult to evaluate the effect of long-term hyperglycemia in a research setting because of the disease's slow progression Hn this study, we u sed streptozotocin (30 mg/kg of body weight, intravenously) to induce a state of chronic hyperglycemia in eight cynomolgus monkeys, and comp ared these monkeys with a matched control group (n = 8), Seven of eigh t monkeys with streptozotocin-induced diabetes required insulin therap y to avoid ketosis. After disease induction, all diabetic monkeys had significantly higher preprandial plasma glucose and glycated hemoglobi n values, compared with their baseline values or values for control mo nkeys. Diabetic monkeys also had abnormal responses to an intravenous glucose tolerance test, Consistent with the chronic hyperglycemic stat e and formation of advanced glycation end products, diabetic monkeys h ad a significant increase in skin fluorescence over the course of the 6-month study, Plasma triglyceride and cholesterol concentrations incr eased, but not significantly so, in the diabetic monkeys after disease induction and were not significantly different from concentrations in control monkeys, Six months after disease induction, monkeys were nec ropsied, and immunohistochemical staining for insulin in the pancreati c islets indicated that diabetic monkeys had a significantly decreased amount of staining for the hormone. The percentage of islet insulin s taining was significantly correlated with physiologic responses to the postinduction intravenous glucose tolerance test in all monkeys, Beca use cynomolgus monkeys are well-characterized models of atherosclerosi s, this model may be useful for determining mechanisms whereby diabete s mellitus increases cardiovascular disease.