Expression of Adiponectin Receptor mRNA in Human Skeletal Muscle Cells Is Related to In Vivo Parameters of Glucose and Lipid Metabolism

Expression of Adiponectin Receptor mRNA in Human Skeletal Muscle Cells Is Related to In Vivo Parameters of Glucose and Lipid Metabolism Harald Staiger , Simone Kaltenbach , Katrin Staiger , Norbert Stefan , Andreas Fritsche , Alke Guirguis , Claudia Péterfi , Melanie Weisser , Fausto Machicao , Michael Stumvoll and Hans-Ulrich Häring From the Department of Endocrinology, Metabolism, and Pathobiochemistry, Medical Clinic Tübingen, Eberhard-Karls-University, Tübingen, Germany Address correspondence and reprint requests to Prof. Dr. med. Hans-Ulrich Häring, Department of Internal Medicine IV, Medical Clinic Tübingen, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany. E-mail: hans-ulrich.haering{at}med.uni-tuebingen.de Abstract 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/μg 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 β-cells needs to be further clarified. AdipoR, adiponectin receptor AMPK, AMP-activated protein kinase ISI, insulin sensitivity index OGTT, oral glucose tolerance test Footnotes H.S. and S.K. contributed equally to this work. Accepted May 26, 2004. Received November 20, 2003. DIABETES