Effects of Recombinant Human IGF-I/IGF-Binding Protein-3 Complex on Glucose and Glycerol Metabolism in Type 1 Diabetes

Saukkonen, Tero; Shojaee-Moradie, Fariba; Williams, Rachel M.; Amin, Rakesh; Yuen, Kevin C.; Watts, Angie; Acerini, Carlo L.; Umpleby, A. Margot; Dunger, David B.
August 2006
Diabetes;Aug2006, Vol. 55 Issue 8, p2365
Academic Journal
Recombinant human IGF-I (rhIGF-I) complexed with its natural binding protein IGF-binding protein (IGFBP)-3 (rhIGF-I/IGFBP-3) is a novel formulation that has been shown to improve insulin sensitivity in type 1 diabetes, yet the mechanisms are not clear. We used stable isotopes to investigate the effects of rhIGF-I/IGFBP-3 on glucose and glycerol metabolism in type 1 diabetes. Fifteen subjects (age 13-24 years; 10 males) were studied on three occasions in random order. Each study period lasted for two days, and an injection of either placebo or rhIGF-I/IGFBP-3 (0.1-0.8 mg â‹… kg-1 â‹… day-1) was given subcutaneously at 6:00 P.M. on days 1 and 2. Following the second injection, the subjects were kept euglycemic overnight by a variable rate insulin infusion, followed by a 4-h, two-step (insulin 0.6 and 1.5 mU â‹… kg-1 â‹… min-1) hyperinsulinemic-euglycemic clamp. During the overnight basal steady state, rhIGF-I/ IGFBP-3 dose-dependently reduced endogenous glucose production rate (Ra) (P = 0.004), while peripheral glucose uptake (Rd) was not different from placebo. The increase in glucose Rd during hyperinsulinemic clamp was greater following rhIGF-I/IGFBP-3 than placebo, both during the first (P = 0.008) and second step (P = 0.008) of the clamp. No significant differences were found in glycerol Ra, a measure of lipolysis, between rhIGF-I/IGFBP-3 and placebo. In conclusion, rhIGF-I/IGFBP-3 enhances glucose metabolism by controlling both endogenous glucose output and peripheral glucose uptake. Diabetes 55:2365-2370, 2006


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