Skeletal muscle 11beta 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 11betaHSD1. We aimed to investigate the changes of SkM 11betaHSD1 enzyme activity and mRNA expression, relative to plasma cortisol, insulin and glucose levels following elective abdominal surgery.


METHODS
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 11betaHSD1 and H6PDH mRNA levels were measured by quantitative RT-PCR and enzyme activity by % conversion of (3)H cortisone to cortisol. Plasma glucose, insulin, free fatty acids (FFA), tumour necrosis factor-alpha and cortisol by standardised assays.


RESULTS
Compared with baseline, SkM 11betaHSD1 activity was significantly increased on day 5 after surgery (14.7+/-2.1 vs 20.4+/-3.2%, P=0.005). Neither 11betaHSD1 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 SkM 11betaHSD1 activity in response to a physiological stressor. Sustained activation of this enzyme may increase tissue cortisol bioactivity.
Jang
Christina
C
Department of Endocrinology and Diabetes, St Vincent's Hospital, Melbourne Department of Medicine, University of Melbourne 41 Victoria Parade, Fitzroy 3065, Australia.
Obeyesekere
Varuni R
VR
Alford
Frank P
FP
Inder
Warrick J
WJ
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000005:Abdomen / Q000601:surgery; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002763:Cholecystectomy; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation / Q000502:physiology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D006854:Hydrocortisone