Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects

Thongchai Pratipanawatr, Wilailak Pratipanawatr, Clifford Rosen, Rachele Berria, Mandeep Bajaj, Kenneth Cusi, Lawrence Mandarino, Sangeta Kashyap, Renata Belfort, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty acid (FFA) and glucose metabolism were compared in eight control and eight type 2 diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and 0.5 mU·kg-1. min-1) clamp and a two-step euglycemic IGF-I (26 and 52 pmol·kg1·min-1) clamp with [3-3H]glucose, [1-14C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (Rd) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of Rd (second clamp step) in response to both insulin and IGF-I was reduced by ∼40-50% compared with control subjects. In control subjects, insulin was more effective than IGF-I in suppressing endogenous glucose production (EGP) during both clamp steps. In type 2 diabetic subjects, insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF-I was similar to that of controls. In both control and diabetic subjects, IGF-I-mediated suppression of plasma FFA concentration and inhibition of FFA turnover were markedly impaired compared with insulin (P < 0.01-0.001). During the second IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was impaired in diabetic vs. control subjects (P < 0.05-0.01). Conclusions: 1) IGF-I is less effective than insulin in suppressing EGP and FFA turnover; 2) insulin-resistant type 2 diabetic subjects also exhibit IGF-I resistance in skeletal muscle. However, suppression of EGP by IGF-I is not impaired in diabetic individuals, indicating normal hepatic sensitivity to IGF-I.

Original languageEnglish (US)
Pages (from-to)E1360-E1368
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume282
Issue number6 45-6
DOIs
StatePublished - 2002

Keywords

  • Free fatty acid metabolism
  • Insulin resistance
  • Insulin-like growth factor I
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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