The Effects of Acute Hypercortisolemia on β-Hydroxybutyrate and Glycerol Metabolism During Insulin Deficiency

Summary

The present study was undertaken to determine whether an acute physiologic rise in plasma cortisol during selective insulin deficiency would have significant effects on glycerol and β-hydroxybutyrate metabolism in conscious overnight-fasted dogs. Each experiment consisted of a two hour dye equilibration period, a 40 minute basal period, and a 3 hour experimental period. A continuous infusion of indocyanine green dye for blood flow estimation was initiated at the start of the equilibration period and continued throughout the experiment. In both of two protocols selective insulin deficiency was created during the experimental period by infusing somatostatin peripherally (0.8 μg/kg-min) with basal replacement of glucagon intraportally (0.65 ng/ kg-min). In the test protocol (CORTISOL, n = 5), 3.0 μg/kg-min of hydrocortisone was infused during the experimental period. In the control protocol (SALINE, n = 5), saline was infused. Net hepatic balances were determined using the (A-V) difference technique. During selective insulin deficiency alone (SALINE), the arterial blood glycerol level increased from 81 ± 19 to 140 ± 11 μM (p<0.01) and net hepatic glycerol uptake (NHGlyU) tended to increase from 2.3 ± 0.3 to 3.3 ± 0.6 μmol/kg-min (0.05<0.1). The arterial plasma free fatty acid (FFA) level remained unchanged at 1041 ± 35 μM. The arterial β-hydroxybutyrate (BHOB) level increased slightly from 21 ± 4 to 29 ± 5 μM while net hepatic β-hydroxybutyrate production (NHBP) remained unchanged (1.0 ± 0.2 μmol/kg-min). During acute hypercortisolemia with selective insulin deficiency (CORTISOL), similar changes occurred in the arterial blood glycerol level and net hepatic glycerol uptake. The arterial plasma FFA level remained unchanged at 1214 ± 105 ±μM. However, the BHOB level increased from 19 ± 3 to 67 ± 10 μM while NHBP increased from 1.1 ± 0.1 to 2.8 ± 0.6 μmol/kg-min. These results suggest that an acute physiologic rise in plasma cortisol during insulin deficiency can markedly enhance ketogenesis and that this enhancement occurs independently of changes in lipolysis.

Key words

Cortisol - β-Hydroxybutyrate - Glycerol - Insulin Deficiency