Hepatic 11β-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique.
OBJECTIVE
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-(2)H3]cortisol (D cortisol) and [4-(13)C]cortisone ([(13)C]cortisone) were ingested, while [1,2,6,7-(3)H]cortisol ([(3)H] cortisol) was infused intravenously to enable concurrent measurements of first-pass hepatic extraction of ingested D cortisol and hepatic conversion of ingested [(13)C]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 [(13)C]cortisone to C13 cortisol was similar between groups.


CONCLUSIONS
Hepatic conversion of [(13)C]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.
Endocrine Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo College of Medicine, Joseph 5-194, 200 First Street, SW, Rochester, MN, 55905, USA.
Simmi
S
Dube
Barbara
B
Norby
Vishwanath
V
Pattan
Ravi K
RK
Lingineni
Ravinder J
RJ
Singh
Rickey E
RE
Carter
Ananda
A
Basu
Rita
R
Basu
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology*
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1