Hepatic 11β-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique

Simmi Dube, Barbara Norby, Vishwanath Pattan, Ravi K. Lingineni, Ravinder J. Singh, Rickey E. Carter, Ananda Basu, Rita Basu

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Aims/hypothesis: Dysregulation of 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme activities are implicated in the pathogenesis of obesity and insulin resistance. The aim of the study was to determine whether hepatic 11β-HSD type 1 (11β-HSD-1) enzyme activity differs in people with and without obesity and type 2 diabetes. Methods: We measured hepatic 11β-HSD-1 activity in the overnight fasted state in 20 lean non-diabetic participants (LND), 21 overweight/obese non-diabetic participants (OND) and 20 overweight/obese participants with type 2 diabetes (ODM) using a non-invasive approach. One mg doses of [9,12,12-2H3]cortisol (D cortisol) and [4-13C]cortisone ([13C]cortisone) were ingested, while [1,2,6,7-3H]cortisol ([3H] cortisol) was infused intravenously to enable concurrent measurements of first-pass hepatic extraction of ingested D cortisol and hepatic conversion of ingested [ 13C]cortisone to C13 cortisol derived from the ingested cortisone (a measure of 11β-HSD-1 activity in the liver) using an isotope dilution technique. One-way ANOVA models and Kruskal-Wallis tests were used to test the hypothesis. Results: Plasma D cortisol and C13 cortisol concentrations were lower in OND than in LND (p<0.05) over 6 h of the study. There was no difference (p=0.15) in C13 and D cortisol concentrations between OND and ODM and between LND and ODM for the same study period. Hepatic conversion of [ 13C]cortisone to C13 cortisol was similar between groups. Conclusions/interpretation: Hepatic conversion of [13C]cortisone to C13 cortisol did not differ between the groups studied. We conclude that hepatic 11β-HSD-1 activity is similar in individuals who are overweight/obese or who have type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)1446-1455
Number of pages10
JournalDiabetologia
Volume57
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • 11β-Hydroxysteroid dehydrogenase
  • Diabetes
  • Obesity

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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