Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis

Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis. Circulating RBP4 levels were measured in 19 patients with liver cirrhosis at different clinical stages of the disease and in 20 age-, sex- and body mass index (BMI)-matched controls. Hepatic production rates of RBP4 and glucose were assessed by measuring the arterial hepatic venous concentration difference together with hepatic blood flow. Insulin resistance was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) and the homeostasis model assessment of insulin resistance (HOMA-IR), energy expenditure by indirect calorimetry and body composition by bioelectrical impedance analysis (BIA). Compared with controls, RBP4 levels in cirrhosis were decreased (8.1 +/- 1.8 vs. 22.6 +/- 2.4 mg/l, P < 0.001) due to decreased hepatic production (P < 0.05). RBP4 correlated with hepatic protein synthesis capacity (P < 0.01), but not with insulin resistance, energy expenditure, BMI or body fat mass. Plasma RBP4 correlated with hepatic glucose production (P < 0.05). These data demonstrate that RBP4 in cirrhosis (i) is decreased due to reduced hepatic production, (ii) is not associated with insulin resistance, and (iii) might have a beneficial role by decreasing hepatic glucose production and could thus also be regarded as a hepatokine.