The Pathophysiology of Experimental Insulin-Deficient Diabetes in the Monkey

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Abstract
In an 11-yr study of experimental insulin-deficient diabetes (IOD) induced in rhesus monkeys by streptozotocin or total pancreatectomy, pathophysiologic changes occur in eye and kidney, which closely resemble the early stages of human insulin-deficient diabetes mellitus (IDDM). In addition, morphologic changes of thickening of glomerular capillary basement membrane and expansion of mesangial matrix (by light microscopy) appear within 3 yr of onset of hyperglycemia. Progression to irreversible complications of advanced diabetic nephropathy or proliferative retinopathy, have not occurred. This animal model resembles human disease in that the animals tend to become ketotoxic unless maintained with exogenous insulin; C-peptide production is low to absent, and large amounts of glycosylated hemoglobin develop within a month of onset. The monkeys differ from humans in the absence of hypertension and hyperlipidemia. Apparently the abnormalties in basement membrane form and function caused by hyperglycemia form the necessary background upon which other factors, such as hypertension and hyperlipidemia, then act to cause irreversible complications. The role of pancreatic transplantation is in prevention of these background changes.