Chronic Hyperinsulinemia Does Not Increase the Production Rate of High-Density Lipoprotein Apolipoprotein AI

Abstract

Objective— In vitro studies showed that insulin stimulates the production of apolipoprotein AI (apoAI). Thus, we hypothesized that chronic hyperinsulinemia could contribute to the increase in the production of high-density lipoprotein apoAI that is observed in metabolic syndrome. Approach and Results— We performed an in vivo kinetic study with stable isotope in 7 patients with insulinoma who showed hyperinsulinemia but no insulin resistance, 8 patients with insulin resistance, and 16 controls. Insulinemia was 3.1× ( P <0.01) higher in patients with insulinoma or insulin resistance than in controls in the fasting state and, respectively, 3.5× and 2.6× ( P <0.05) higher in the fed state. The high-density lipoprotein apoAI pool size was smaller in patients with insulin resistance than in controls (49.3±5.4 versus 59.6±7.7 mg·kg −1 ; P <0.01), whereas both the high-density lipoprotein apoAI fractional catabolic rate and the high-density lipoprotein apoAI production rate were higher (0.30±0.07 versus 0.20±0.04 pool·d −1 ; P <0.0001 and 14.6±1.5 versus 11.5±1.9 mg·kg −1 ·d −1 ; P <0.01, respectively). In contrast, no significant difference was observed for these parameters between patients with insulinoma and controls. In patients with insulinoma, the apoAI pool size tended to be greater than in patients with insulin resistance (56.3±8.6 versus 49.3±5.4 mg·kg −1 ; P =0.078), whereas both the apoAI fractional catabolic rate and the production rate were lower (0.20±0.06 versus 0.30±0.07 pool·d −1 ; P <0.01 and 11.1±1.6 versus 14.6±1.5 mg·kg −1 ·d −1 ; P <0.01, respectively). The apoAI fractional catabolic rate was the only variable associated with the apoAI production rate in multivariate analysis and explained 80% of its variance. Conclusions— Chronic endogenous hyperinsulinemia does not induce any increase in the apoAI production rate, which seems to be more dependent on the apoAI fractional catabolic rate.