Skeletal muscle 11β hydroxysteroid dehydrogenase type 1 activity is upregulated following elective abdominal surgery

Objective: Cortisol has been traditionally implicated in the causation of peri-operative skeletal muscle (SkM) insulin resistance, but cortisol levels return to normal within 72 h of surgery. Tissue cortisol bioactivity may be prolonged by local upregulation of the enzyme 11 beta HSD1 We aimed to investigate the changes of SkM 11 beta HSD1 enzyme activity and mRNA expression, relative to plasma cortisol, insulin and glucose levels following elective abdominal surgery. Patients and design: Eight non-diabetic subjects (two male, six female) underwent serial plasma hormone sampling and muscle biopsy of vastus lateralis at baseline and on day 5 following elective laparoscopic cholecystectomy. Methods: SkM 11 beta beta HSD1 and H6PDH mRNA levels were measured by quantitative RT-PCR and enzyme activity by % conversion of H-3 cortisone to cortisol. Plasma glucose. insulin, free fatty acids (FFA), tumour necrosis factor-alpha and cortisol by standardised assays. Results: Compared with baseline, SkM 11 beta HSD1 activity was significantly increased on day 5 after surgery (14.7 +/- 2.1 vs 20.4 +/- 3.2%, P=0.005). Neither 11 beta HSD1 nor H6PDH mRNA levels were altered after surgery. Plasma cortisol (P=0.027), FFA (P=0.01) and glucose (P=0.004) rose rapidly following surgery and had returned to baseline values by 24 h post-surgery. There was no significant change in plasma insulin. Conclusions: This is the first Study to demonstrate an upregulation of SkM11 beta HSD1 activity in response to a physiological stressor. Sustained activation of this enzyme may increase tissue cortisol bioactivity.