Circulating retinol-binding protein-4, insulin sensitivity, insulin secretion, and insulin disposition index in obese and nonobese subjects

OBJECTIVE - Recent investigations disclosed an upregulation of retinol-binding protein-4 (RBP4) in the adipose tissue of several insulin-resistant mouse models and increased serum RBP4 concentration in subjects with obesity and type 2 diabetes in association with insulin rest. stance. There is some experimental evidence that RBP4 also could been linked to insulin secretion. RESEARCH DESIGN AND METHODS - We aimed to evaluate insulin secretion, insulin sensitivity, insulin disposition index (minimal model analysis), and circulating RBP4 (enzyme-linked immunosorbent assay) in nondiabetic men with a wide range of obesity (n = 107). RESULTS - Serum RBP4 concentration was nonsignificantly different among lean, overweight, and obese subjects. Circulating RBP4 was not associated with age, BMI, waist-to-hip ratio, or metabolic parameters, including insulin sensitivity (r = -0.03, P = 0.6). On the contrary, circulating RBP4 was negatively associated with insulin secretion, especially in obese subjects (r = -0.48, P = 0.007), in whom RBP4 also was linked to insulin disposition index (r = -0.44, P = 0.01). On multiple regression analyses to predict insulin secretion (acute insulin response [AIR(g)]), insulin sensitivity was the only factor that contributed to 17% of AIR(g) variance in nonobese subjects. in obese subjects, however, RBP4 emerged as an independent factor that contributed independently to AIR(g) variance (23%). CONCLUSIONS - Our results suggest that oversecretion of RBP4 may negatively affect beta-cell function directly or by preventing the binding of transthyretin to its receptor. These mechanisms could be behind the association between increased circulating RBP4 and type 2 diabetes. RBP4 could be one signal from insulin-resistant tissues that impacts on P-cell secretion.