FOREARM SUBSTRATE EXCHANGE DURING HYPERINSULINEMIC HYPOGLYCEMIA IN NORMAL MAN

To assess muscle substrate exchange during hypoglycaemia, 8 healthy young male subjects were studied twice during 2 h of hyperinsulinaemic euglycaemia followed by 4 h of (1) hypoglycaemia (plasma glucose < 2.8 mmol l(-1)), and (2) euglycaemia. Insulin was infused at a rate of 1.5 mU kg(-1) min(-1) throughout. When compared to euglycaemia, hypoglycaemia was associated with: (1) increment in circulating glucagon (65 +/- 8 vs 23 +/- 4 ng l(-1), p < 0.05), growth hormone (19.9 +/- 3.6 vs 2.6 +/- 1.3 mu g l(-1), p < 0.05), adrenaline (410 +/- 88 vs 126 +/- 32 ng l(-1), p < 0.05) and increased suppression of C-peptide (0.5 +/- 0.1 vs 1.0 +/- 0.1 mu g l(-1), p < 0.05) along with a modest lowering of insulin (103 +/- 10 vs 130 +/- 13 mU l(-1), p < 0.05); (b) decrease in plasma glucose level (3.0 +/- 0.07 vs 5.0 +/- 0.12 mmol l(-1), p < 0.05), forearm glucose uptake (0.21 +/- 0.09 vs 1.21 +/- 0.21 mmol l(-1), p < 0.05) and requirement for exogenous glucose (5.61 +/- 1.1 vs 13.2 +/- 0.9 mg kg(-1) min(-1) p < 0.005) together with an impaired suppression of isotopically determined endogenous glucose production (0.34 +/- 0.5 vs -2.3 +/- 0.3 mg kg(-1) min(-1), p < 0.05); (3) exaggerated increase in blood lactate (1680 +/- 171 vs 1315 +/- 108 mu mol l(-1), p < 0.05) and a decrease in alanine (215 +/- 18 vs 262 +/- 19 mu mol l(-1), p < 0.05). Forearm release of lactate (130 +/- 43 vs 12 +/- 31 mu mol l(-1), p = 0.09) tended to be increased, whereas alanine balance (18 +/- 6 vs 17 +/- 5 mu mol l(-1)) was unchanged. (4) Total forearm blood flow increased similarly during both studies (4.4 +/- 0.6 vs 4.2 +/- 0.5 ml 100 ml(-1) min(-1)). These data suggest that the human forearm is not a major site for glucose uptake nor for lactate production during protracted hypoglycaemia; the fact that forearm glucose uptake is reduced sixfold during hypoglycaemia further suggests that restriction of glucose uptake in muscles plays a frontline role in the defence against hypoglycaemia.