EFFECTS OF INSULIN ON THE COUNTERREGULATORY RESPONSE TO EQUIVALENT HYPOGLYCEMIA IN NORMAL FEMALES

The aim of this study was to determine if insulin could augment the co unterregulatory response to equivalent hypoglycemia in normal females similarly to males. Experiments were carried out in nine normal lean o vernight-fasted female subjects. Insulin was infused in two separate r andomized protocols so that steady-state levels of 794 +/- 62 (low) an d 3,620 +/- 476 pM (high) were obtained. Despite an identical plasma g lucose level (2.8 +/- 0.1 mM), epinephrine (5.7 +/- 0.9 vs. 3.9 +/- 0. 6 nM), norepinephrine (2.7 +/- 0.4 vs. 1.8 +/- 0.3 nM), cortisol (918 +/- 55 vs. 826 nM), and growth hormone (35.8 +/- 3.7 vs. 28.4 +/- 2.7 mug/l) were increased (P < 0.05) during high compared with low insulin infusion, respectively. Glucagon and pancreatic polypeptide levels in creased significantly but were not different during the two insulin in fusions. Hepatic glucose production was increased during the high- com pared with low-dose infusions (9.5 +/- 1.1 vs. 5.1 +/- 2.2 mumol - kg- 1 . min-1; P < 0.05). Lipolysis, as indicated by the blood glycerol le vel, increased significantly during high- compared with low-dose insul in infusions (121 +/- 29 vs. 65 +/- 13 muM; P < 0.05). The hormonal an d metabolic responses to hypoglycemia were significantly different in females compared with previous results in males. During the high-dose infusion when there was similar hyperinsulinemia and glycemia, epineph rine (5.7 +/- 0.8 vs. 8.8 +/- 0.7 nM), norepinephrine (2.6 +/- 0.4 vs. 3.3 +/- 0.3 nM), glucagon (127 +/- 25 vs. 215 +/- 24 ng/l), growth ho rmone (36 +/- 4 vs. 53 +/- 6 mug/l), pancreatic polypeptide (144 +/- 4 6 vs. 291 +/- 53 pM), and hepatic glucose production (9.5 +/- 1.1 vs. 18.1 +/- 1.1 mumol . kg-1 . min-1) were reduced (P < 0.05) in females compared with males. Cortisol (919 +/- 55 vs. 811 +/- 36 nM) and glyce rol (124 +/- 28 vs. 72 +/- 13 muM) were, on the other hand, increased (P < 0.05) in females. We conclude that 1) in normal females, similar to males, hyperinsulinemia can amplify the counterregulatory response to equivalent hypoglycemia by increasing catecholamine, cortisol, grow th hormone secretion, hepatic glucose production, and lipolysis and 2) there are distinct quantitative gender-related differences in hormona l and metabolic responses to insulin-induced hypoglycemia.