Abstract

Objective: Retinol-binding protein 4 (RBP4) is an adipokine of which plasma levels are elevated in obesity and type 2 diabetes. The aims of the study were to identify determinants of plasma RBP4 and RBP4 mRNA expression in subcutaneous adipose tissue (SAT) and skeletal muscle, and to investigate the association between RBP4 and in vivo measures of glucose metabolism.

Research Design and Methods: The study populations included 298 elderly twins (62-83 years) with glucose tolerance ranging from normal to overt type 2 diabetes, and 178 young (25-32 years) and elderly (58-66 years) non-diabetic twins. Peripheral and hepatic insulin sensitivity was assessed by a euglycemic, hyperinsulinemic clamp, and β-cell function was estimated from an intravenous glucose tolerance test.

Results: The influence of environmental versus genetic factors in the regulation of plasma RBP4 increased with age. Plasma RBP4 was elevated in type 2 diabetes and increased with duration of disease. Plasma RBP4 correlated inversely with peripheral, but not hepatic, insulin sensitivity. However, the association disappeared after correction for covariates, including plasma adiponectin. Plasma retinol, and not RBP4, was inversely associated with insulin secretion. SAT RBP4 expression correlated positively with GLUT4 expression and inversely with glucose tolerance. Skeletal muscle RBP4 expression reflected intramuscular fat, and although suppressed by insulin, no association to insulin sensitivity was evident. RBP4 expression was not associated with circulatory RBP4.

Conclusion: In conclusion, our data indicate that RBP4 levels in plasma, skeletal muscle and fat may be linked to insulin resistance and type 2 diabetes in a secondary and non-causal manner.

Abbreviations: AU: Arbitrary units, DZ: Dizygotic, ELISA: Enzyme-linked immunosorbent assay, FFM: Fat-free mass, FOX: Insulin stimulated fat oxidation rate, GOX: Insulin stimulated glucose oxidation rate, HGP: Hepatic glucose production, MZ: Monozygotic, OGTT: Oral glucose tolerance test, RBP4: Retinol-binding protein 4, R_d: Insulin-stimulated glucose disposal rate, SAT: Subcutaneous adipose tissue, SD: Standard deviation