Altered activity of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in skeletal muscle confers metabolic protection in subjects with type 2 diabetes.

CONTEXT

There is little information regarding the regulation of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes in skeletal muscle in the setting of type 2 diabetes.

OBJECTIVE

Our objective was to investigate whether there is differential mRNA expression and enzyme activity of 11beta-HSD1 and 11beta-HSD2 in the skeletal muscle of diabetic subjects compared with controls at baseline and in response to dexamethasone.

DESIGN

Participants underwent muscle biopsy of vastus lateralis at baseline and after dexamethasone.

SETTING

The study took place at a university teaching hospital.

PARTICIPANTS

Twelve subjects with type 2 diabetes and 12 age- and sex-matched controls participated.

INTERVENTION

Subjects were given oral dexamethasone, 4 mg/d for 4 d.

MAIN OUTCOME MEASURES

We assessed 11beta-HSD1, 11beta-HSD2, and H6PDH mRNA levels by quantitative RT-PCR and enzyme activity by percent conversion of [(3)H]cortisone and [(3)H]cortisol, respectively.

RESULTS

At baseline, mRNA levels were similar in diabetic and control subjects for 11beta-HSD1, 11beta-HSD2, and H6PDH. 11beta-HSD1 activity was reduced in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 11.4 +/- 2.5% vs. 18.5 +/- 2.2%; P = 0.041), and 11beta-HSD2 enzyme activity was higher in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 17.2 +/- 2.6% vs. 9.2 +/- 1.3%; P = 0.012). After dexamethasone, 11beta-HSD1 mRNA increased in both groups (P < 0.001), whereas 11beta-HSD2 mRNA decreased (P = 0.002). 11beta-HSD1 activity increased in diabetic subjects (P = 0.021) but not in controls, whereas 11beta-HSD2 activity did not change in either group. At baseline, there was a significant negative correlation between 11beta-HSD1 and 11beta-HSD2 enzyme activity (r = -0.463; P = 0.026).

CONCLUSIONS

The activities of skeletal muscle 11beta-HSD1 and 11beta-HSD2 are altered in diabetes, which together may reduce intracellular cortisol generation, potentially conferring metabolic protection.