Streptozotocin Diabetes in the Monkey: Plasma Levels of Glucose, Insulin, Glucagon, and Somatostatin, with Corresponding Morphometric Analysis of Islet Endocrine Cells

Abstract

Streptozotocin (STZ) was administered to 20 female rhesus monkeys at a dose of between 30 and 55 mg/kg. Depending on the severity of the resultant diabetic-like state, these animals were divided into two groups: insulin-dependent monkeys requiring daily insulin injections and carbohydrate-disturbed animals not requiring insulin. STZ-treated monkeys exhibited significantly higher fasting glucose levels or increased glucose disappearance times after an intravenous glucose tolerance test than did controls. In the insulin-dependent monkeys, fasting plasma glucagon levels were elevated when compared with the carbohydrate-disturbed or control monkeys. Glucagon levels did not differ between carbohydrate-disturbed and control animals. Fasting somatostatin levels were also significantly elevated in insulin-dependent animals when compared with controls. Morphometric analysis was performed on the alpha, beta, and delta cell populations of the pancreatic islets in three control and three diabetic animals. Significant decreases in beta cell percent volume and numerical percent and increases in both alpha and delta cell percent volume and numerical percent were observed in relation to control values after STZ diabetes lasting from 17 to 31 mo. Thus, the diabetic-like state induced by STZ in the monkey resembles juvenile-onset human diabetes mellitus with respect to plasma hormone levels and to morphometric changes in the islets of Langerhans.