Forearm Substrate Exchange during Hyperinsulinaemic Hypoglycaemia 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 μg 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 μg 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 (5.6 ± 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 μmol l −1 , p < 0.05) and a decrease in alanine (215 ± 18 vs 262 ± 19 μmol l −1 , p < 0.05). Forearm release of lactate (130 ± 43 vs 12 ± 31 μmol l −1 , p = 0.09) tended to be increased, whereas alanine balance (18 ± 6 vs 17 ± 5 μmol 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.