The adiponectin receptors, AdipoR1 and AdipoR2, are thought to transmit the insulin-sensitizing, anti-inflammatory, and atheroprotective effects of adiponectin. In this study, we examined whether AdipoR mRNA expression in human myotubes correlates with in vivo measures of insulin sensitivity. Myotubes from 40 metabolically characterized donors expressed 1.8-fold more AdipoR1 than AdipoR2 mRNA (588 +/- 35 vs. 321 +/- 39 fg/microg total RNA). Moreover, the expression levels of both receptors correlated with each other (r = 0.45, P < 0.01). AdipoR1 mRNA expression was positively correlated with in vivo insulin and C-peptide concentrations, first-phase insulin secretion, and plasma triglyceride and cholesterol concentrations before and after adjustment for sex, age, waist-to-hip ratio, and body fat. Expression of AdipoR2 mRNA clearly associated only with plasma triglyceride concentrations. In multivariate linear regression models, mRNA expression of AdipoR1, but not AdipoR2, was a determinant of first-phase insulin secretion independent of insulin sensitivity and body fat. Finally, insulin did not directly modify myotube AdipoR1 mRNA expression in vitro. In conclusion, we provide evidence that myotube mRNA levels of both receptors are associated with distinct metabolic functions but not with insulin sensitivity. AdipoR1, but not AdipoR2, expression correlated with insulin secretion. The molecular nature of this link between muscle and beta-cells needs to be further clarified.