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-[3-3H]glucose, L-[U-14C]alanine, and indocyanine green dye were used to assess glucose production (Ra) and gluconeogenesis using tracer and arteriovenous (a-v) difference techniques. In the cortisol group, (n = 10), a continuous infusion of hydrocortisone (3.5 micrograms.kg-1 x 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 microU/ml. Glucose Ra was elevated in the cortisol group (3.5 +/- 0.2 vs. 2.8 +/- 0.2 mg.kg-1 x min-1) but net hepatic glucose output was markedly diminished (1.2 +/- 0.4 vs. 2.7 +/- 0.3 mg.kg-1 x 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 x 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 nonhepatic 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.
Goldstein
R E
RE
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Wasserman
D H
DH
McGuinness
O P
OP
Lacy
D B
DB
Cherrington
A D
AD
Abumrad
N N
NN
D020155:3-Hydroxybutyric Acid; D000409:Alanine / Q000378:metabolism; D000818:Animals; D001158:Arteries; D001786:Blood Glucose / Q000032:analysis; D050260:Carbohydrate Metabolism; D004285:Dogs; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood*; D006885:Hydroxybutyrates / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D013997:Time Factors
D001786:Blood Glucose; D006885:Hydroxybutyrates; D007773:Lactates; D019344:Lactic Acid; D006003:Glycogen; D005947:Glucose; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D006854:Hydrocortisone