From the Faculté de Médecine, INSERM U866-Université de Bourgogne, Dijon, France (L.D., E.F., F.P., J.-M.P., B.V.); Laboratoire de Biologie Médicale, CHU, Dijon, France (L.D., E.F.); Service d'Endocrinologie et Maladies Métaboliques, CHU, Dijon, France (J.-M.P. S.B.-R., B.V.); and Service d'Endocrinologie et Maladies Métaboliques, CHU, Besançon, France (A.P.).
Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2460-5. doi: 10.1161/ATVBAHA.113.301597. Epub 2013 Aug 1.
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.
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.
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.
体外研究表明胰岛素可刺激载脂蛋白 AI（apoAI）的生成。因此，我们推测在代谢综合征中观察到的高密度脂蛋白 apoAI 生成增加可能与慢性高胰岛素血症有关。
我们对 7 例表现为高胰岛素血症但无胰岛素抵抗的胰岛素瘤患者、8 例胰岛素抵抗患者和 16 例对照者进行了稳定同位素的体内动力学研究。空腹时，胰岛素瘤或胰岛素抵抗患者的胰岛素血症分别比对照组高 3.1 倍（P<0.01）和 3.5 倍（P<0.05）；进食时，胰岛素瘤或胰岛素抵抗患者的胰岛素血症分别比对照组高 2.6 倍（P<0.05）和 2.6 倍（P<0.05）。胰岛素抵抗患者的高密度脂蛋白 apoAI 池大小明显小于对照组（49.3 ± 5.4 与 59.6 ± 7.7 mg·kg(-1)；P<0.01），而高密度脂蛋白 apoAI 分解代谢率和生成率均较高（0.30 ± 0.07 与 0.20 ± 0.04 池·d(-1)；P<0.0001 和 14.6 ± 1.5 与 11.5 ± 1.9 mg·kg(-1)·d(-1)；P<0.01）。相反，胰岛素瘤患者与对照组之间这些参数无显著差异。胰岛素瘤患者的 apoAI 池大小大于胰岛素抵抗患者（56.3 ± 8.6 与 49.3 ± 5.4 mg·kg(-1)；P=0.078），而 apoAI 分解代谢率和生成率均较低（0.20 ± 0.06 与 0.30 ± 0.07 池·d(-1)；P<0.01 和 11.1 ± 1.6 与 14.6 ± 1.5 mg·kg(-1)·d(-1)；P<0.01）。多元分析显示，apoAI 分解代谢率是 apoAI 生成率的唯一相关变量，解释了其 80%的变异性。
慢性内源性高胰岛素血症不会引起 apoAI 生成率的任何增加，apoAI 生成率似乎更依赖于 apoAI 分解代谢率。
