Adrenergic mechanisms contribute to the late phase of hypoglycemic glucose counterregulation in humans by stimulating lipolysis

Abstract

Three studies were performed on nine normal volunteers to assess whether catecholamine-mediated lipolysis contributes to counterregulation to hypoglycemia. In these three studies, insulin was intravenously infused for 8 h (0.30 mU · kg-1 · min-1 from 0 to 180 min, and 0.40 mU · kg-1 · min-1 until 480 min). In study I (control study), only insulin was infused; in study II (direct + indirect effects of catecholamines), propranolol and phentolamine were superimposed to insulin and exogenous glucose was infused to reproduce the same plasma glucose (PG) concentration of study I. Study III (indirect effect of catecholamines) was the same as study II, except heparin (0.2 · kg-1 · min-1 after 80 min), 10% Intralipid (1 ml · min-1 after 160 min) and variable glucose to match PG of study II, were also infused. Glucose production (HGO), glucose utilization (Rd) [3-3H]glucose, and glucose oxidation and lipid oxidation (LO) (indirect calorimetry) were determined. In all three studios, PG decreased from ≈ 4.8 to ≈ 2.9 mmol/liter (P = NS between studies), and plasma glycerol and FFA decreased to a nadir at 120 min. Afterwards, in study I plasma glycerol and FFA increased by ≈ 75% at 480 min, but in study II they remained ≈ 40% lower than in study I, whereas in study III they rebounded as in study I (P = NS). In study II, LO was lower than in study I (1.69±0.13 vs. 3.53±0.19 μmol · kg-1 · min-1, P < 0.05), whereas Rd was greater between 210 and 480 min (19±0.38 vs. 11.4±0.34 μmol · kg-1 · min-1, respectively, P < 0.05). In study III, LO increased to the values of study I; between 4 and 8 h, HGO increased by ≈ 2.5 μmol · kg-1 · min-1, and Rd decreased by ≈ 7 μmol · kg-1 · min-1 vs. study II. We conclude that, in a late phase of hypoglycemia, the indirect effects of catecholamines (lipolysis mediated) account for at least ≈ 50% of the adrenergic contribution to increased HGO, and ≈ 85% of suppressed Rd.