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

Abstract

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. Conclusions/interpretation: 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.

Acute and selective regulation of glyceroneogenesis and cytosolic phosphoenolpyruvate carboxykinase in adipose tissue by thiazolidinediones in type 2 diabetes

“…The second important observation from our present study is that rosiglitazone administration to type 2 diabetes patients for 12 weeks induced PCK1 mRNA, but not PCK2 mRNA, in s.c. adipose tissue at a much higher incremental level than that of any other gene tested in the same cohort [8,40,41]. Similar results were obtained by Bogacka et al in a cohort of pioglitazone-treated type 2 diabetes patients [22].…”

Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state

“…Thus, Tan et al 36 could not find any correlation between APM1 expression and receptor expression in subcutaneous abdominal fat of patients with DM2. Rasmussen et al 29 on the other hand, reported higher expression of AdipoR1 than AdipoR2 in both SAT and VAT in a group of obese non-diabetic women.…”

Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study

“…specifically, adiponectin could control insulin sensitivity mainly by modulating non-oxidative glucose disposal, i.e. the glycogen synthesis pathway in human skeletal muscle (50). It is interesting to note that plasma adiponectin levels correlated significantly with FFA levels at baseline, and during rosiglitazone treatment, the changes of adiponectin and clamp FFA concentrations were significantly and negatively associated.…”