Nonhuman Primates as Models for the Study of Human Diabetes Mellitus

Abstract

Nonhuman primates have been used for a variety of studies on diabetes meiiitus. Spontaneous, natural forms of diabetes have been well documented in several species; there are limited data on numerous other species that indicate diabetes or a diabetes-like syndrome. The causes and manifestations of spontaneous diabetes, their prevalence, and their severity vary among species. Diabetes has also been induced in nonhuman primates with streptozotocin, alloxan, hypothalamic lesions, or pancreatectomy. The extent and severity of metabolic and hormonal abnormalities vary according to the method of induction, the individual monkey, and the species. Metabolic, hormonal, and pathologic abnormalities present in human diabetics also occur in monkeys with either spontaneous or induced diabetes. Hyperglcemia, and impaired glucose clearance are common, lipid concentrations are elevated, and hemoglobin A1c concentrations are increased in Hyperglycemic monkeys. Monkeys may have fasting hypo- or hyperinsulinemia; insulin responses are often impaired in glucose tolerance tests. Glucagon concentrations may be increased. Aortic atherosclerosis, muscle capillary microangiopathies, cataracts, and glomeruio-sclerosis have been documented. Primate size and longevity allow longitudinal studies with procedures that may not be feasible in smaller animals or in human beings. Nonhuman primates may be the models of choice for studies on selected aspects of diabetes and its secondary complications.

Diabetes-Induced Accelerated Atherosclerosis in Swine

“…Consequently, these studies frequently lacked suitable controls that consumed nonatherogenic diets or atherogenic diets alone (42), and they did not compare atherogenesis in diabetic and nondiabetic conditions. However, such studies have demonstrated severe atherosclerosis in diabetic animals (42)(43)(44), accompanied by atherogenic lipid profiles (42,47), which are in keeping with the present findings. Review of the literature has revealed no detailed studies on atherosclerosis in diabetic swine.…”

“…These models have proven useful for studies on numerous aspects of diabetes, but they are poor models of diabetic atherosclerosis, as they develop nonhumanoid lesions, at best, and have lipid and lipoprotein metabolism and profiles very different from humans. A more successful approach has been the superimposition of ␤-cell ablation (by pancreatectomy or use of the diabetogenic agents alloxan and STZ) on animal models of atherosclerosis, including nonhuman primates (42)(43)(44) and rabbits (45). Surprisingly, few studies of the effects of chemically induced diabetes on atherosclerosis have been carried out in humanoid models, and these have largely been performed as part of other studies in nonhuman primates.…”

A novel primate model of delayed wound healing in diabetes: dysregulation of connective tissue growth factor

“…This animal model of streptozotocin-induced diabetes has been well characterised [22,23] and develops complications comparable with those occurring in human diabetes [19,21]. Animals have diabetes duration of greater than 10 years.…”

Ultrastructural Analysis of Major Basement Membrane Types in Rhesus Monkey <i>Macaca mulatta</i> Acellular Renal Cortex

“…1972;Bloodwortli et al, 1973;Howard, 1982;Jones et al, 1984], few studies have focused on the ultrastructural features of these components of the extracellular matrix (ECM) in normal monkey kidneys.…”

“…Rhesus monkeys (Macaca mulatta) have been particularly useful in the development of models of renal disease [Chase et al, 1972;Smith and Roberts, 1978;Richmun et al. 1980], most notably spontaneous [DiGiacomo et al, 1971;Heiberg, 1982;Howard, 1982] and experimental [Bloodwortli et al. 1973;Schien et al, 1973] diabetes mellitus, in which many of the renal changes considered pathognomon ic for the disease in the human have been described.…”