Skeletal muscle glucose uptake, glycogen synthase activity and GLUT 4 content during hypoglycaemia in type 1 diabetic subjects

In healthy subjects, hypoglycaemia induces a profound 80% reduction in skel etal muscle glucose uptake and a similar suppression of glycogen synthase a ctivity. The aim of this study was to examine the efficacy of this counterr egulatory mechanism in type 1 diabetic subjects, who are especially prone t o hypoglycaemic incidents. Nine type 1 diabetic male subjects were examined twice; during 120 min of hyperinsulinaemic (1.5mU.kg(-1).min(-1)) euglycae mia followed by (i) 240min of graded hypoglycaemia (glucose nadir 2.8 mM) o r (ii) 240 min of euglycaemia. At 345-360min a muscle biopsy was taken and indirect calorimetry was performed at 210-240 and 320-340min. The sensitivi ty of glycogen synthase to glucose-6-P was reduced by hypoglycaemia, as sho wn by an increase in A0.5 for glucose-6-P (at 0.07mmol/L) from 0.21 +/-0.02 to 0.28 +/-0.03 mM (p=0.06). Likewise, the fractional velocity for glycoge n synthase was reduced by 25%; i.e. from 20.8 +/-2.0 to 15.5 +/-1.4% (p<0.0 5). Total glucose disposal was decreased during hypoglycaemia (5.3<plus/min us>0.6 vs. 8.3 +/-0.7mg.kg(-1).min(-1) (euglycaemia), n=9; p<0.05), primari ly due to a reduction of non-oxidative glucose disposal (2.7<plus/minus>0.3 vs. 5.1 +/-0.6 mg.kg(-1).min(-1) (euglycaemia), n=7; p<0.05), Forearm arte riovenous glucose differences were decreased by 50% in the hypoglycaemic si tuation (0.7<plus/minus>0.1 vs. 1.4 +/-0.3 mmol/L (320-340min)), and counte rregulatory hormonal responses seemed less conspicuous than described in he althy subjects. We conclude that hypoglycaemia induces decrements of forear m glucose uptake and glycogen synthase activity in type 1 diabetic subjects . The study indicates a decreased magnitude of these responses, but this re mains to be confirmed.