The effects of acute elevations in plasma cortisol levels on alanine metabolism in the conscious dog

Abstract

The present study was undertaken to determine whether an acute physiological increase in plasma cortisol level had significant effects on alanine metabolism and gluconeogenesis within 3 hours in conscious, overnight-fasted dogs. Each experiment consisted of an 80-minute tracer and dye equilibration period, a 40-minute basal period, and a 3-hour experimental period. A primed, continuous infusion of [3- 3H]glucose and continuous infusions of [U- 14C]alanine and indocyanine green dye were initiated at the start of the equilibration period and continued throughout the experiment. Dogs were studied with (1) a hydrocortisone infusion ([CORT] 3.0 μg · kg −1 · min −1, n = 5), (2) hydrocortisone infused as in CORT, but with pancreatic hormones clamped using somatostatin and basal intraportal replacement of insulin and glucagon (CLAMP + CORT, n = 5), or (3) saline infusion during a pancreatic clamp (CLAMP, n = 5). Glucose production and gluconeogenesis were determined using tracer and arteriovenous difference techniques. During CLAMP, all parameters were stable except for a modest 67% ± 6% increase in gluconeogenic conversion of alanine to glucose and a 53% ± 26% increase in gluconeogenic efficiency. When plasma cortisol levels were increased fourfold during CLAMP + CORT, there was no change in the concentration, production, or clearance of glucose. Gluconeogenic conversion of alanine to glucose increased 10% ± 34% and gluconeogenic efficiency increased 65% ± 43%, while net hepatic alanine uptake (NHAU) increased 60% ± 19% and hepatic fractional extraction of alanine increased 38% ± 12%. Cortisol did not cause an increase in the arterial glycerol level or net hepatic glycerol uptake. When plasma cortisol levels were increased and the pancreatic hormones were allowed to change (CORT), there was a transient but significant decrease in plasma insulin levels, while plasma glucagon levels remained unchanged. There was no change in the concentration, production (R a), or clearance of glucose. However, gluconeogenic conversion of alanine increased 190% ± 59%, gluconeogenic efficiency increased 57% ± 43%, NHAO increased 75% ± 25%, and hepatic alanine fractional extraction increased 48% ± 6%. These changes were all statistically significant by the first 90 minutes of hydrocortisone infusion. In addition, there was a tendency for both net hepatic production of lactate and net hepatic uptake of glycerol to be elevated compared with the other two groups. These results suggest that an acute physiologic increase in plasma cortisol level can increase the gluconeogenic conversion of alanine to glucose by increasing both NHAU and hepatic fractional extraction of alanine. This increase in plasma cortisol level may also be associated with a transient decrease in plasma insulin level that may further promote gluconeogenesis.