The Effects of Differing Insulin Levels on the Hormonal and Metabolic Response to Equivalent Hypoglycemia in Normal Humans

Abstract

The aim off this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia in normal humans. Experiments were conducted in 9 normal, lean men, who had fasted overnight. Insulin was infused in two separate, randomized protocols so that steady-state levels of 486 ± 33 (low) and 3056 ± 236 pM (high) were obtained. Glucose was infused during both protocols to ensure that the rate of fall of plasma glucose (0.07 mM/min) and hypoglycemic plateau (2.8 ± 0.1 mM) were similar. Despite similar plasma glucose levels, EPI (8.7 ± 0.7 vs. 5.5 ± 0.7 nM), NE (3.3 ± 0.3 vs. 2.3 ± 0.2 nM), and cortisol (811 ± 36 vs. 611 ± 72 nM) significantly increased during high compared with low insulin infusion, respectively (P < 0.05). Glucagon, growth hormone, and pancreatic polypeptide levels increased briskly and significantly but were not different during the two insulin infusions. HGP rose significantly from 12.1 ± 0.3 to 18.1 ± 1.1 μmol · kg⁻¹ · min⁻¹ in response to the high insulin level (P < 0.05) but remained unchanged (12.1 ± 0.4 and 11.7 ± 1.4 μmol · kg⁻¹ · min⁻¹) in the presence of the low insulin level. GRa increased significantly during high insulin levels (3.4 ± 0.3 to 4.8 ± 0.7 μmol · kg⁻¹ · min⁻¹ P < 0.05) but remained at a basal rate (3.0 ± 0.3 to 2.7 ± 0.6 μmol · kg⁻¹ · min⁻¹) in the presence of low insulin levels. sBP and heart rate increased more during high insulin infusion (18 ± 5 vs. 6 ± 5 mmHg and 18 ± 4 vs. 7 ± 2 beats/min, respectively, P < 0.05). In summary, the 6-fold higher insulin level resulted in significantly greater increases in catecholamine and cortisol secretion, HGP, lipolysis, heart rate, and sBP despite equivalent hypoglycemia. We conclude that at moderate hypoglycemia, high doses of insulin can augment certain aspects of the counterregulatory response in normal humans.