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

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/g 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 ␤-cells needs to be further clarified.

Regulation of adiponectin receptors in hepatocytes by the peroxisome proliferator-activated receptor-γ agonist rosiglitazone

“…In a study of a Mexican-American population, the expression levels of ADIPOR1 and ADIPOR2 in skeletal muscles and the plasma adiponectin concentration were lower in people with a family history of type 2 diabetes than in those without the family history [27]. This is consistent with the fact that the expression levels of both adiponectin receptors in human skeletal muscle cells were related to distinct in vivo parameters of glucose and lipid metabolism [28]. Genetic studies in an Old-Order Amish population also revealed that genetic variations in both adiponectin receptors, including the 5′ promoter regions, are associated with type 2 diabetes [29].…”

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

“…Interestingly, we observed that refeeding carbohydrate did not change adipoR1 or adipoR2 expression in humans. Other studies in humans have shown that the adipoR1/R2 expression is not changed after insulin infusion (44) or after insulin addition to primary muscle culture (45). Together, these findings strongly suggest that adipoR expression is not regulated by glucose or insulin in humans.…”

Adiponectin resistance and vascular dysfunction in the hyperlipidemic state

“…Similarly, Inukai and colleagues [72] found that insulin had an inhibitory effect on AdipoR1 expression, in a mechanism mediated by the PI3K-dependent pathway rather than the MAPK pathway. In contrast to Inukai, Staiger and colleagues [73] reported that insulin did not directly modify AdipoR1 mRNA expression in human skeletal muscle cells. These discrepancies may be due to differences in animal model, cell types, or conditions used in these various studies.…”