INSULIN-LIKE GROWTH FACTOR-I IN NONINSULIN-DEPENDENT DIABETIC MONKEYS - BASAL PLASMA-CONCENTRATIONS AND METABOLIC EFFECTS OF EXOGENOUSLY ADMINISTERED BIOSYNTHETIC HORMONE

Plasma insulin-like growth factor-I (IGF-I) concentrations and the effects of exogenous IGF-I administration were determined in 26 rhesus monkeys; each animal was well characterized regarding its degree of obesity, plasma glucose and insulin levels, and glucose tolerance (KG). Five separate groups were identified: lean normal, obese normoinsulinemic and normoglycemic, obese hyperinsulinemic with normal glucose tolerance, impaired glucose tolerant, and spontaneously diabetic (type II, non-insulin-dependent diabetes mellitus [NIDDM]). Basal plasma IGF-I levels in all monkeys ranged from 249 to 1,093 ng/mL and were strongly associated with age (r = -.66; P < .001) and KG (r = .59; P < .001), but not with body weight, body fat, or fasting plasma glucose or insulin levels. In addition, the acute insulin-like effects of exogenously administered IGF-I on glucose disappearance were studied in vivo in a dose-response comparison to insulin (subcutaneous administration of IGF-I at doses of 50, 100, or 200 μg/kg v insulin at 0.3 U/kg). Five hyperinsulinemic normoglycemic monkeys (fasting plasma glucose, 67 ± 2 mg/dl; insulin, 163 ± 42 μU/mL) and overt type II diabetic monkeys (fasting plasma glucose, 201 ± 13 mg/dL; insulin, 38 ± 6 μU/mL) each underwent a series of three to five experiments to determine the time course and degree of hypoglycemia induced by IGF-I as compared with insulin or with control (saline) injection. Results showed that a 200 μg/kg IGF-I dose produced significant hypoglycemic effects (38% ± 8% decrease in plasma glucose) in the diabetic animals, while the 0.3 U/kg insulin dose led to a 62% ± 5% decrease in plasma glucose. The hypoglycemia induced by IGF-I was of slower onset and longer duration (time of nadir, 228 ± 20 v 174 ± 26 minutes, IGF-I and insulin, respectively). Furthermore, in the hyperinsulinemic monkeys, IGF-I led to a consistent and sustained decrease in plasma insulin levels before a decrease in plasma glucose. These results in rhesus monkeys clearly document the relationship of IGF-I to age and diabetes in an animal model with spontaneous, obesity-associated NIDDM. In addition, these studies are the first to demonstrate the consistent and sustained glucose-lowering effects of IGF-I as compared with insulin in overtly non-insulin-dependent diabetic subjects. These results suggest that IGF-I may be useful as an additional element in the clinical management of type II diabetes. © 1991.