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 counterregulatory response to equivalent hypoglycemia in normal females similarly to males. Experiments were carried out in nine normal lean overnight-fasted female subjects. Insulin was infused in two separate randomized protocols so that steady-state levels of 794 +/- 62 (low) and 3,620 +/- 476 pM (high) were obtained. Despite an identical plasma glucose 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 increased significantly but were not different during the two insulin infusions. Hepatic glucose production was increased during the high- compared 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 level, increased significantly during high- compared with low-dose insulin infusions (121 +/- 29 vs. 65 +/- 13 muM; P < 0.05). The hormonal and 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, epinephrine (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 hormone (36 +/- 4 vs. 53 +/- 6 mug/l), pancreatic polypeptide (144 +/- 46 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 glycerol (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, growth hormone secretion, hepatic glucose production, and lipolysis and 2) there are distinct quantitative gender-related differences in hormonal and metabolic responses to insulin-induced hypoglycemia.