Adiponectin, skeletal muscle adiponectin receptor expression and insulin resistance following dexamethasone.
OBJECTIVE
Skeletal muscle is a major site of adiponectin action and of glucocorticoid-induced insulin resistance. Little human data exist however, regarding the impact of exogenous glucocorticoids on adiponectin receptors in skeletal muscle.


METHODS
Twelve subjects with type 2 diabetes and 12 controls underwent blood sampling and muscle biopsy of vastus lateralis before and after 4 days of 4 mg dexamethasone.


METHODS
(i) Total and high molecular weight (HMW) plasma adiponectin, glucose and insulin; (ii) Skeletal muscle adiponectin receptor AdipoR1 and AdipoR2 mRNA levels by quantitative real time RT-PCR.


RESULTS
Baseline total adiponectin (8.0 +/- 0.89 vs. 12.5 +/- 1.46 microg/ml, P = 0.013), HMW adiponectin (2.8 +/- 0.44 vs. 5.9 +/- 1.04 microg/ml, P = 0.014) and AdipoR2 mRNA levels (mean DeltaC(T )14.71 +/- 0.35 vs. 13.37 +/- 0.28, P = 0.017) were significantly lower in diabetic subjects. After dexamethasone, AdipoR2 mRNA fell in the controls but there was no change in the diabetic group, while there was a significant increase in total (P = 0.002) and HMW adiponectin (P < 0.001) across both groups. Total and HMW plasma adiponectin correlated with clinical and biochemical measures of insulin sensitivity. However following dexamethasone which increased insulin resistance, the relationship between adiponectin and the biochemical measures was lost.


CONCLUSIONS
Plasma adiponectin and skeletal muscle AdipoR2 mRNA expression are reduced in subjects with diabetes; both are likely to contribute to the observed insulin resistance. Dexamethasone inhibits AdipoR2 mRNA expression in nondiabetic subjects, while there is a small rise in plasma adiponectin levels. The close relationship between plasma adiponectin and biochemical measures of insulin sensitivity is lost in the setting of glucocorticoid-induced insulin resistance.
Jang
Christina
C
Department of Endocrinology and Diabetes, St Vincent's Hospital, Melbourne, Australia. christina.jang@svhm.org.au
Inder
Warrick J
WJ
Obeyesekere
Varuni R
VR
Alford
Frank P
FP
D052242:Adiponectin / Q000097:blood*; D001706:Biopsy; D003907:Dexamethasone / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000378:metabolism
D052242:Adiponectin; D020033:Protein Isoforms; D054419:Receptors, Adiponectin; D003907:Dexamethasone