INSULIN-LIKE GROWTH-FACTOR-I LEVELS DECREASE IN THE DEVELOPMENT OF DIABETES IN MACACA-NIGRA

Members of the monkey species Macaca nigra spontaneously develop impai rments in insulin secretion and glucose clearance, and eventually beco me overtly diabetic. Changes in certain metabolic signals such as clea rance of glucose and insulin increment secreted in an intravenous gluc ose tolerance test have allowed the identification of four stages in t he progression from non-diabetes to diabetes in monkeys - non-diabetic , hormonally impaired, borderline diabetic, and diabetic. Recently, an other metabolic stage, hyperinsulinemic, was also identified in these animals. In recent years, other factors besides those listed above hav e been implicated to be correlated with the metabolic progression from a nondiabetic to a diabetic state. One of these factors, is insulin l ike growth factor I (IGF-I). In diabetic humans who are in poor metabo lic control, and in rats with streptozotocin induced ketotic diabetes, serum levels of IGF-I are lowered by as much as 40-50% of control non -diabetics. If indeed decreased IGF-I levels are correlated with the o nset of diabetes then changes in IGF-I concentrations prior to the cli nically diagnosed disease state would be expected. Using serum samples collected from different animals in a colony of Macaca nigra in a var iety of metabolic states, we have found that IGF-I and insulin levels decrease in each defined metabolic state as the animals progress from nondiabetic to diabetic. Since IGF-I and insulin levels decrease in a similar fashion in the progression of this disease then this maybe ind icative of the coordinate expression of these two factors.