Effects of chronic hypercortisolemia on carbohydrate metabolism during insulin deficiency
Goldstein, R.E.; Cherrington, A.D.; Reed, G.W.; Lacy, D.B.; Wasserman, D.H.; Abumrad, N.N.
American Journal of Physiology 266(4 Pt 1): E618-E627
1994
ISSN/ISBN: 0002-9513 PMID: 8178983 Document Number: 434391
This study was undertaken to further investigate the effect of acute selective insulin deficiency on glycogenolysis and gluconeogenesis occurring during chronic physiological hypercortisolemia in conscious overnight fasted dogs. After an 80-min tracer and dye equilibration period and a 40-min basal period, selective insulin deficiency was created during the 180-min experimental period by infusing somatostatin peripherally (0.8 mu-g cntdot kg-1 cntdot min-1) with basal replacement of glucagon intraportally (0.65 ng cntdot kg-1 cntdot min-1). In the cortisol group (n = 5), a continuous infusion of hydrocortisone (3.5 mu-g cntdot kg-1 cntdot min-1) was begun 5 days before the experiment. In the saline group (n = 5), there was no infusion of cortisol. (3-3H)glucose, (U-14C)alanine. and indocyanine green dye were used to assess glucose production and gluconeogenesis using tracer and arteriovenous difference techniques. During selective insulin deficiency in the saline group, the arterial plasma glucose level (Glc) increased from 109 +- 2 to 285 +- 19 mg/dl; glucose production increased from 2.7 +- 0.2 to 4.5 +- 0.3 mg cntdot kg-1 cntdot min-1. Gluconeogenic efficiency and conversion of alanine to glucose (Conv) increased by 300 +- 55 and 356 +- 67%. During selective insulin deficiency, in the cortisol group, Glc increased from 117 +- 3 to 373 +- 50 mg/dl; glucose production increased from 3.3 +- 0.5 to 6.9 +- 0.7 mg cntdot kg-1 min-1. Gluconeogenic efficiency and Conv increased by 268 +- 41 and 393 +- 75%, respectively. The maximal glycogenolytic rate increased significantly more in the cortisol group than in the saline group, accounting for the difference in glucose production. These results suggest that, even during chronic hypercortisolemia, acute insulin deficiency has more pronounced effects on glycogenolysis than gluconeogenesis.