Naturally occurring and experimental diabetes in cynomolgus monkeys: A comparison of carbohydrate and lipid metabolism and islet pathology

Diabetes is a major health problem of increasing incidence in the United St ates. Diabetes research has been limited by lack of availability of good an imal models, particularly for the study of comorbidities associated with di abetes. We investigated the use of cynomolgus monkeys as an animal model of both type 1 and type 2 diabetes and compared these naturally occurring dis eases with streptozotocin-induced diabetes. Both type I diabetics and strep tozotocin-induced diabetics present with sudden onset of hyperglycemia and are ketosis prone without exogenous insulin. Type 2 diabetics can have a ve ry long period of moderate hyperglycemia and hypertriglyceridemia and only require exogenous insulin therapy if pancreatic islet reserves are depleted . Type 2 diabetes is preceded by a relatively long period of insulin resist ance that is associated with obesity and dyslipidemia. As insulin resistanc e progresses, islet size and insulin content increases initially. However, with sustained periods of insulin resistance, islet amyloid polypeptide (IA PP) is deposited in islets and can replace normal islet architecture, resul ting in an insulin-deficient state. Appearance of IAPP also occurs in human type 2 diabetics but not in conventional rodent models. Unlike type 2 diab etes, neither type 1 nor streptozotocin-induced diabetes is associated with IAPP. Rather, islets can appear normal histologically, but have decreased insulin secretion and immunostaining. Further, the amount of insulin presen t in the islet is correlated with plasma insulin levels following glucose c hallenge. Studies are ongoing to determine the pathogenic changes associate d with the progression of diabetes and to find novel drug treatments for di abetics.