Effects of recombinant human IGF-I/IGF-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes

Tero Saukkonen, Fariba Shojaee-Moradie, Rachel M. Williams, Rakesh Amin, Kevin C. Yuen, Angie Watts, Carlo L. Acerini, A. Margot Umpleby, David B. Dunger

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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·kg-1·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·kg-1·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.

Original languageEnglish (US)
Pages (from-to)2365-2370
Number of pages6
JournalDiabetes
Volume55
Issue number8
DOIs
StatePublished - Aug 1 2006

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Keywords

  • IGFBP, IGF-binding protein
  • NEFA, nonesterified fatty acid
  • rHIGF-I, recombinant human IGF-I

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Saukkonen, T., Shojaee-Moradie, F., Williams, R. M., Amin, R., Yuen, K. C., Watts, A., Acerini, C. L., Umpleby, A. M., & Dunger, D. B. (2006). Effects of recombinant human IGF-I/IGF-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes. Diabetes, 55(8), 2365-2370. https://doi.org/10.2337/db05-1646