Insulin-mediated increase in glucose 1,6-bisphosphate is attenuated in skeletal muscle of insulin-resistant man.

The purpose of this study was to determine the effect of insulin infusion on the glucose 1,6-bisphosphate (glucose 1,6-P2) content in skeletal muscle of insulin resistant man. Euglycemic (approximately 100 mg/dL) hyperinsulinemic clamps were performed on seven men with chronically elevated fasting plasma glycemia (228 +/- 13 mg/dL, mean +/- SE) who were insulin resistant (HIR) and five men with normal fasting glycemia (115 +/- 5 mg/dL) who were insulin resistant (NIR). Insulin was infused at successive rates of 40 and 400 mU/m2/min, and biopsies were obtained from the quadriceps femoris muscle before and after insulin infusion. The results were compared with those of normoglycemic insulin-sensitive (NIS) men. The insulin-resistant groups had significantly higher percent body fat values than did the NIS group. Glucose 1,6-P2 increased from 70 +/- 6, 49 +/- 9, and 67 +/- 3 mumols/kg dry weight in the basal state to 135 +/- 12 (P less than .001 v basal), 67 +/- 11 (P greater than .05) and 79 +/- 3 (P greater than .05) after 40 mU insulin in NIS, HIR, and NIR, respectively. Glucose 1,6-P2 increased to 147 +/- 12 (P less than .001 v basal), 91 +/- 15 (P less than .01) and 99 +/- 13 (P less than .05) mumols/kg dry weight after 400 mU insulin in NIS, HIR, and NIR, respectively. The increase in glucose 1,6-P2 in response to 40 mU insulin was only 28% and 18% in HIR and NIR, respectively, of that in NIS.(ABSTRACT TRUNCATED AT 250 WORDS)