Impact of Type 1 Diabetes and Insulin Treatment on Plasma Levels and Fractional Synthesis Rate of Retinol-Binding Protein 4

Abstract

Retinol binding protein 4 (RBP4) levels are elevated in insulin-resistant states and reduced in type 1 diabetes (T1D), but it is unknown whether changes in insulin levels and glycemic control alter RBP4 levels. In vivo synthesis rates of RBP4 and their relationship to RBP4 levels remain to be determined. The aim of the study was to determine whether the synthesis rate of RBP4 is altered in people with T1D during both insulin deficiency and insulin treatment. Seven T1D participants were studied on two occasions, during 8 h of insulin deprivation and during insulin treatment, and compared with nondiabetic (ND) controls. We measured in vivo fractional synthesis rate of RBP4 using [ring-(13)C(6)]phenylalanine as a tracer and RBP4 concentration in plasma by nephelometric assay and Western blot analyses. Plasma RBP4 levels were lower (P < 0.01) in insulin-treated T1D than in ND but were not different between insulin-deprived T1D and ND participants. Synthesis rates of RBP4 in ND (2.46 +/- 0.29%/h) were higher than in insulin-treated T1D (1.45 +/- 0.21) (P = 0.02), but there was no difference between ND and insulin-deprived T1D (2.24 +/- 0.24). Glucose levels were not different between ND and insulin-treated T1D, but insulin levels were higher in insulin-treated T1D (82.8 +/- 2 pmol/liter) than in ND (28.7 +/- 6) and insulin-deprived T1D (4.6 +/- 1.6) (P < 0.01). Insulin treatment that achieved normoglycemia but relative hyperinsulinemia was associated with lower RBP4 synthesis and levels in T1D. Short-term insulin deprivation and hyperglycemia had no effect on RBP4 levels and synthesis rates in T1D.