Changes in adiponectin receptor expression in muscle and adipose tissue of type 2 diabetic patients during rosiglitazone therapy

Aims/hypothesis: Adiponectin is important in the regulation of insulin sensitivity in man. Its receptors, adipoR1 and R2, have recently been identified, but their expression in adipose tissue and their regulation in response to insulin sensitisation of diabetic patients have never been assessed. We therefore explored the regulation of adipoR1/R2 and adiponectin expression in adipose tissue and skeletal muscle, and of adiponectin plasma concentrations in response to insulin sensitisation by rosiglitazone. Methods: Patients with type 2 diabetes were studied in a double-blind, placebo-controlled crossover study, using in vivo arteriovenous techniques of measuring adipose tissue and muscle blood flow, combined with measurement of adipose tissue and skeletal muscle gene expression. Results: Rosiglitazone treatment increased adiponectin concentrations by 69%. Skeletal muscle adipoR1 expression was down-regulated from 109.0 (70.1-165.7) (median [interquartile range]) to 82.8 (63.6-89.3) relative units (p=0.04), but adipose tissue adipoR1 expression was up-regulated from 5.3 (4.4-9.4) to 11.2 (4.8-15.3) relative units (p=0.02) by rosiglitazone. In contrast to adipoR1 expression, adipoR2 expression was not altered by rosiglitazone in either of the tissues. The increase in adipose tissue adipoR1 expression with rosiglitazone was associated with increased postprandial triglyceride clearance (r=0.67, p=0.05), and increased fasting fatty acid output (r=0.78, p=0.01) measured in subcutaneous adipose tissue. Conclusion: AdipoR1 expression is up-regulated in adipose tissue but down-regulated in skeletal muscle by rosiglitazone. These data suggest that adipoR1 plays a role in mediating the effects of adiponectin in specific tissues in relation to insulin sensitisation.