Glucocorticoid excess increases hepatic 11β-HSD-1 activity in humans: Implications in steroid-induced diabetes

Simmi Dube, Michael Q. Slama, Ananda Basu, Robert A. Rizza, Rita Basu

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Context: Animal studies indicate that glucocorticoids increase hepatic 11-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) expression and activity. Objective: Our goal was to determine whether glucocorticoid excess increases cortisol production in the liver via 11-HSD-1 enzyme pathway in humans. Design: A total of 1 mg each [4-13C] cortisone and [9,12,12-2H3] cortisol were ingested, and [1,2,6,7-3H] cortisol was infused to measure C13 cortisol (derived from ingested [4-13C] cortisone) turnover using the triple tracer technique, whereas glucose turnover was measured using isotope dilution technique following [6-62H2] glucose infusion during a saline clamp. Setting: This study took place at the Mayo Clinic Clinical Research Unit. Participants: Thirty nondiabetic healthy subjects participated. Intervention: Subjects were randomized to hydrocortisone (n = 15) or placebo 50 mg twice daily (n = 15) for 1 week. Outcome Measures: Hepatic cortisol production and endogenous glucose production were measured. Results: Plasma cortisol concentrations were higher throughout the study period in hydrocortisone group. Rates of appearance of C13 cortisol and hepatic C13 cortisol production were higher in hydrocortisone vs placebo group, indicating increased hepatic 11β-HSD-1 activity. Higher plasma cortisol and presumably higher intrahepatic cortisol was associated with impaired suppression of endogenous glucose production in hydrocortisone vs placebo group. Conclusion: Chronic glucocorticoid excess increases intrahepatic cortisone to cortisol conversion via the 11β-HSD-1 pathway. The extent to which this causes or exacerbates steroid induced hepatic insulin resistance remains to be determined.

Original languageEnglish (US)
Pages (from-to)4155-4162
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

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