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Circulating Retinol-Binding Protein-4, Insulin Sensitivity, Insulin Secretion, and Insulin Disposition Index in Obese and Nonobese Subjects

¹ Reseach Unit, Pere Virgili Institute for Biomedical Research, Tarragona, Spain
² CIBER Fisiopatología Obesidad y Nutrición CB06/03/0011, Instituto de Salud Carlos III, Hospital Joan XXII, Tarrogona, Spain
³ Diabetes, Endocrinology and Nutrition Unit, Dr. Josep Trueta Hospital, Girona, Spain
⁴ Girona Institute for Biomedical Research and CIBER Fisiopatología Obesidad y Nutrición CB06/03/0010, Instituto de Salud Carlos III, Girona, Spain

Address correspondence and reprint requests to José Manuel Fernández-Real, MD, Unit of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Av. Francia s/n, 17007 Girona, Spain. E-mail: uden.jmfernandezreal{at}htrueta.scs.es

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 resistance. 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 ß-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 ß-cell secretion.

Abbreviations: AIR, acute insulin response • ELISA, enzyme-linked immunosorbent assay • RBP4, retinol-binding protein-4 • TTR, transthyretin

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