COUNTERREGULATION IN PERIPHERAL-TISSUES - EFFECT OF SYSTEMIC HYPOGLYCEMIA ON LEVELS OF SUBSTRATES AND CATECHOLAMINES IN HUMAN SKELETAL-MUSCLE AND ADIPOSE-TISSUE

We used microdialysis to distinguish the effects of hyperinsulinemia a nd hypoglycemia on glucose, gluconeogenic substrate, and catecholamine levels in adipose and muscle extracellular fluid (ECF). Ten lean huma ns (six males and four females) were studied during baseline and hyper insulinemic (3 mU . kg(-1) . min(-1) for 3 h) euglycemia (5.0 mmol/l) and hypoglycemia (2.8 mmol/l). In muscle and adipose, basal ECF glucos e was lower (muscle, 3.5 +/- 0.2 mmol/l; adipose tissue, 3.3 +/- 0.2 m mol/l) and lactate was higher (muscle, 2.2 +/- 0.2 mmol/l; adipose, 1. 5 +/- 0.3 mmol/l) than respective plasma values (glucose, 4.9 +/- 0.1 mmol/l; lactate, 0.7 +/- 0.1 mmol/l), whereas alanine was higher in mu scle ECF (379 +/- 22 mu mol/l) than adipose tissue (306 +/- 22 mu mol/ l) and plasma (273 +/- 33 mu mol/l). Plasma catecholamines (unchanged during euglycemia) rose during hypoglycemia with epinephrine, increasi ng approximately fivefold more than norepinephrine. In contrast, the h ypoglycemia-induced increments in muscle dialysate norepinephrine and epinephrine were similar, suggesting local generation of norepinephrin e. Compared with euglycemia, hypoglycemia produced a greater increase in lactate and a smaller reduction in alanine in muscle ECF, whereas h ypoglycemia caused a greater relative fall in ECF glucose concentratio ns in muscle (72 +/- 16%) and adipose tissue (69 +/- 9%) than in plasm a (42 +/- 3%) (P < 0.05). We conclude that hypoglycemia increases the generation of norepinephrine and gluconeogenic substrates in key targe t tissues, while increasing the plasma-tissue concentration gradient f or glucose. These changes suggest the stimulation of glucose extractio n by peripheral tissues, despite systemic counterregulatory hormone re lease and local sympathetic activation.