Chapter 14 - Diabetes and Obesity Research using Nonhuman Primates

Abstract

Obesity and diabetes are major health problems of increasing incidence. To better study their pathogenesis and find potential therapeutic agents, appropriate animal models are needed. Nonhuman primates (NHPs) are useful models for diabetes. As in humans, Type 2 diabetes mellitus (T2DM) is the most common type of diabetes and occurs in older, obese animals, with a metabolic progression from insulin resistance and impaired glucose tolerance to overt diabetes. Histopathologic changes in pancreatic islets are similar to those seen in humans with diabetes. Initially there is islet hyperplasia with abundant insulin production to compensate for insulin resistance, followed by insufficient insulin production with replacement of islets with islet-associated amyloid. Diabetic NHPs also have detrimental changes in plasma lipid and lipoprotein concentrations, lipoprotein composition, markers of obesity and inflammation, and increased protein glycation due to hyperglycemia. As in humans, all these deleterious changes contribute to exacerbation of atherosclerosis and other complications. Sex hormones and pregnancy have similar effects on insulin resistance in humans and NHPs, and gestational diabetes can occur in NHPs. Environmental factors (e.g., diet, stress) are also important contributors to diabetes progression. Finally, due to the similar clinical and pathologic characteristics of T2DM, NHPs have been used in pharmacological studies to develop new therapeutic agents. Due to their genetic similarity to humans, NHPs may be increasingly used to study gene–environment interactions as they relate to diabetes. Thus, NHPs are a valuable animal model of obesity and diabetes to study disease progression, associated risk factors, and potential treatments.