Context: There is little information regarding the regulation of 11HSD enzymes in skeletal muscle in the setting of Type 2 diabetes.

Objective: To investigate whether there is differential mRNA expression and enzyme activity of 11HSD1 and 11HSD2 in the skeletal muscle of diabetic subjects compared to controls, at baseline and in response to dexamethasone.

Design: Participants underwent muscle biopsy of vastus lateralis at baseline and following dexamethasone.

Setting: University teaching hospital.

Participants: Twelve subjects with Type 2 diabetes and 12 age and sex matched controls.

Intervention: Oral Dexamethasone 4mg per day for 4 days.

Main Outcome Measures: 11HSD1, 11HSD2 and H6PDH mRNA levels by quantitative RT-PCR and enzyme activity by percent conversion of ³H cortisone or cortisol respectively.

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

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