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

Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229-3900 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 · kg 1 · min 1 ) clamp with [3- 3 H]glucose, [1- 14 C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (R d ) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of R d (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