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Relationships of Plasma Adiponectin Level and Adiponectin Receptors 1 and 2 Gene Expression to Insulin Sensitivity and Glucose and Fat Metabolism in Monozygotic and Dizygotic Twins

Steno Diabetes Center (H.S., P.P., A.A.V.), 2820 Gentofte, Denmark; and Department of Clinical Sciences/Diabetes and Endocrinology (C.L., L.G.), Lund University, Clinical Research Centre, University Hospital Malmö, S-205 02 Malmö, Sweden

Address all correspondence and requests for reprints to: Pernille Poulsen, Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. E-mail: pepn{at}steno.dk.

Context: Adiponectin is a key insulin-sensitizing adipokine acting on muscle metabolism via two specific receptors [adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2, respectively)].

Objectives: The aim of the study was to investigate the genetic and nongenetic control of plasma adiponectin and muscle AdipoR1/R2 gene expression and the impact of these components on in vivo glucose and fat metabolism.

Design and Participants: Plasma adiponectin and muscle gene expression of AdipoR1/R2 were measured before and during insulin infusion in 89 young and 69 elderly monozygotic and dizygotic twins. Insulin action, and glucose and fat oxidation rates were determined using hyperinsulinemic euglycemic clamps and indirect calorimetry.

Results: We demonstrated a genetic component in the control of plasma adiponectin and AdipoR1/R2 gene expression. Furthermore, levels of adiponectin and AdipoR1/R2 were influenced by age, sex, abdominal obesity, and aerobic capacity. Intrapair correlations in monozygotic twins indicated a nongenetic influence of birth weight on plasma adiponectin and AdipoR2 expression. Nonoxidative glucose metabolism was associated with AdipoR1 and plasma adiponectin, in young and elderly twins, respectively. In addition, plasma adiponectin was related to glucose and fat oxidation in younger subjects.

Conclusions: Plasma adiponectin and muscle gene expression of its specific receptors are controlled by genetic and several specific nongenetic factors. The data suggest that the "adiponectin axis" plays a role in in vivo insulin action and nonoxidative glucose metabolism.