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

Abstract

The purpose of this study was to determine the effect of insulin infusion on the glucose 1,6-bisphosphate (glucose 1,6-P 2) content in skeletal muscle of insulin resistant man. Euglycemic (∼ 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/m 2/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-P 2 increased from 70 ± 6,49 ± 9, and 67 ± 3 μmol/kg dry weight in the basal state to 135 ± 12 ( P < .001 vbasal), 67 ± 11 ( P > .05) and 79 ± 3 ( P > .05) after 40 mU insulin in NIS, HIR, and NIR, respectively. Glucose 1,6-P 2 increased to 147 ± 12 ( P < .001 v basal), 91 ± 15 ( P < .01) and 99 ± 13 ( P < .05) μmol/kg dry weight after 400 mU insulin in NIS, HIR, and NIR, respectively. The increase in glucose 1,6-P 2 in response to 40 mU insulin was only 28% and 18% in HIR and NIR, respectively, of that in NIS. These data demonstrate that the increase in glucose 1,6-P 2 normally observed in muscle of NIS men in response to insulin is attenuated in muscle of obese, insulin-resistant men. Preliminary results suggest that the attenuated response is not due to obesity per se.