Metabolic Effects of IGF-I in Diabetic Rats

Abstract

Insulinlike growth factor I (IGF-I) stimulates glucose utilization (GU) in nondiabetic rats. We compared the effects of IGF-I and insulin on glucose metabolism in control (fed plasma glucose 7.7 +/- 0.1 mM, n = 30) and partially (90%) pancreatectomized diabetic (plasma glucose 18.4 +/- 0.8 mM, n = 30) awake unstressed rats. IGF-I was infused at 0.65 or 1.96 nmol.kg-1.min-1 and insulin at 22 or 29 pmol.kg-1.min-1 in combination with [3-3H]glucose while euglycemia was maintained by a variable glucose infusion. In controls, GU during the 0.65- and 1.96-nmol.kg-1.min-1 IGF-I infusions (127 +/- 7 and 168 +/- 4 mumol.kg-1.min-1, respectively) was similar to rates observed during the 22- and 29-pmol.kg-1.min-1 insulin infusions (121 +/- 2 and 156 +/- 5 mumol.kg-1.min-1). Whole-body glycolytic rate (3H2O generation) and muscle glycogen synthetic rate were identical during insulin and IGF-I infusions. In diabetic rats, GU was reduced by 30% versus control rats (P less than 0.01) during both the low-dose (88 +/- 7 vs. 121 +/- 7 mumol.kg-1.min-1) and higher-dose (109 +/- 4 vs. 156 +/- 5 mumol.kg-1.min-1) insulin clamps. The defect in insulin action involved both muscle glycogen synthesis and glycolysis. In diabetic rats, IGF-I elicited rates of GU similar to controls (115 +/- 10 and 164 +/- 12 mumol.kg-1.min-1 during the 0.65- and 1.96-nmol.kg-1.min-1 infusions, respectively) and corrected the intracellular defects in glycogen synthesis and glycolysis.(ABSTRACT TRUNCATED AT 250 WORDS)