EFFECTS OF CHRONIC ELEVATION IN PLASMA-CORTISOL ON HEPATIC CARBOHYDRATE-METABOLISM

This study was undertaken to investigate the effects of chronic physiological elevations in plasma cortisol on glycogenolysis and gluconeogenesis in conscious, overnight-fasted dogs. Experiments consisted of an 80-min tracer and dye equilibration period and a 40-min sampling period. Infusions of D-[3-H-3]glucose, L-[U-C-14]alanine, and indocyanine green dye were used to assess glucose production (R(a)) and gluconeogenesis using tracer and arteriovenus (a-v) difference techniques. In the cortisol group, (n = 10), a continuous infusion of hydrocortisone (3.5 mug.kg-1.min-1) was begun 5 days before the experiment and continued throughout the sampling period. In the saline group (n = 10), there was no infusion of cortisol. The fivefold elevation in plasma cortisol increased plasma insulin from 12 +/- 2 to 19 +/- 2 muU/ml. Glucose R(a) was elevated in the cortisol group (3.5 +/- 0.2 vs. 2.8 +/- 0.2 mg.kg-1.min-1) but net hepatic glucose output was markedly diminished (1.2 +/- 0.4 vs. 2.7 +/- 0.3 mg.kg-1. min-1). Gluconeogenic conversion of alanine to glucose was increased slightly by cortisol (0.60 +/- 0.13 to 0.99 +/- 0.12 mumol.kg-1.min-1), but the gluconeogenic efficiency of the liver was unchanged. Cortisol increased hepatic glycogen content evident at the end of the study greater than twofold (76.4 +/- 7.9 vs. 30.0 +/- 4.7 g/liver).These results suggest that cortisol 1) promotes glucose cycling through glycogen, 2) greatly inhibits non-hepatic glucose utilization, 3) increases hepatic gluconeogenesis in vivo primarily through enhanced substrate delivery to the liver, and 4) raises plasma insulin levels, which restrains intrahepatic gluconeogenesis.