Biochemical and histological characterization of chemical-induced diabetes mellitus in the rhesus monkey (Macaca mulatta)

Chronic, insulin-dependent diabetes mellitus was induced in adult rhesus monkeys ( Macaca mulatta ) by the combined administration of a single dose of alloxan (50 mg/kg) and streptozotocin (30 mg/kg). The onset of diabetes was rapid, with symptoms of permanent hyperglycemia, glycosuria, and polyuria occurring within 24–48 hr. Biochemical studies demonstrated minimal insulin secretory capacity in response to several stimulants, including oral and intravenous glucose and intravenous tolbutamide administration. In all of these tests, circulating levels of immunoreactive C-peptide reflected the low levels of insulin, while glucagon levels were consistently elevated compared to preinduction values. Laboratory measurements conducted over a 3-month period revealed minimal toxic effects other than changes associated with the diabetic state. Plasma electrolyte and bicarbonate levels were depressed, whereas serum triglycerides and total lipids were significantly elevated. Glycosylated hemoglobin concentrations were elevated 1 month following diabetes induction, and remained elevated for the duration of the study. The biochemical findings were confirmed by histological alterations in the pancreatic islets. Results of histochemical staining indicated the absence of beta cell granules (insulin) in islets of diabetic monkeys. Pathological evidence of chemical-induced toxicity was not present in other organs. The results of this investigation demonstrated that a single low dose of alloxan-streptozotocin can reliably induce insulin-dependent diabetes mellitus in rhesus monkeys, thereby providing an animal model of this disease in a nonhuman primate.