FOREARM MUSCLE INSULIN-RESISTANCE DURING HYPOGLYCEMIA - ROLE OF ADRENERGIC-MECHANISMS AND HYPOGLYCEMIA PER SE

The forearm perfusion technique was used 1) to quantify the muscle met abolism of glucose and gluconeogenic precursors in response to insulin -induced hypoglycemia and 2) to assess the role of catecholamines and glucose concentration, pe se. Insulin (0.5 mU.kg(-1).min(-1)) was infu sed for 4 h in three groups of healthy volunteers. In group I (n = 6), blood glucose (BG) was maintained at its basal level (4.5 +/- 0.1 mmo l/l). In group II (n = 7), BG was allowed to fall to approximate to 3 mmol/l. Group III (n = 6) was similar to group II except that proprano lol was infused also. In addition, at 240 min, hypoglycemia was locall y corrected by intrabrachial glucose infusion while maintaining the sy stemic milieu unperturbed. In group I, forearm glucose uptake (FGU) in creased from 4.7 +/- 1.3 to a mean value of 37.8 +/- 5.0 mu mol.l(-1). min(-1), whereas in group II it remained unchanged (8.3 +/- 2.0 mu mol .l(-1).min(-1)). In group III, propranolol partially prevented the sup pression of FGU that increased to 21.6 +/- 5.2 mu mol.l(-1).min(-1) (P < 0.05 vs. group II). Local correction of hypoglycemia normalized the FGU response (36.5 +/- 8.0 mu mol.l(-1).min(-1)). Muscle release of l actate, but not of alanine, was slightly higher during hypoglycemia (P = not significant). Forearm blood flow remained unchanged in groups I and III, whereas it increased by similar to 40% in group II (P < 0.05 ). It is concluded that, during mild hypoglycemia 1) extreme insulin r esistance develops in the skeletal muscle, mediated by beta-adrenergic stimulation and reduced glucose mass effect and 2) mobilization of gl uconeogenic precursors is only weakly activated.