Fujita Suguru, Hironaka Ken-Ichi, Karasawa Yasuaki, Kuroda Shinya
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
Department of Biotechnology, Graduate School of Agricultual and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
iScience. 2024 May 16;27(6):109833. doi: 10.1016/j.isci.2024.109833. eCollection 2024 Jun 21.
Insulin plays a crucial role in regulating the metabolism of blood glucose, amino acids (aa), and lipids in humans. However, the mechanisms by which insulin selectively regulates these metabolites are not fully understood. To address this question, we used mathematical modeling to identify the selective regulatory mechanisms of insulin on blood aa and lipids. Our study revealed that insulin negatively regulates the influx and positively regulates the efflux of lipids, consistent with previous findings. By contrast, we did not observe the previously reported insulin's negative regulation of branched-chain aa (BCAA) influx; instead, we found that insulin positively regulates BCAA efflux. We observed that the earlier peak time of lipids compared to BCAA is dependent on insulin's negative regulation of their influx. Overall, our findings shed new light on how insulin selectively regulates the levels of different metabolites in human blood, providing insights into the metabolic disorder pathogenesis and potential therapies.
胰岛素在调节人体血糖、氨基酸(aa)和脂质代谢中起着关键作用。然而,胰岛素选择性调节这些代谢物的机制尚未完全明确。为解决这一问题,我们运用数学建模来确定胰岛素对血液中氨基酸和脂质的选择性调节机制。我们的研究表明,胰岛素对脂质的流入起负调节作用,对脂质的流出起正调节作用,这与先前的研究结果一致。相比之下,我们并未观察到先前报道的胰岛素对支链氨基酸(BCAA)流入的负调节作用;相反,我们发现胰岛素对BCAA的流出起正调节作用。我们观察到,脂质的峰值时间早于BCAA,这取决于胰岛素对其流入的负调节作用。总体而言,我们的研究结果为胰岛素如何选择性调节人体血液中不同代谢物的水平提供了新的线索,有助于深入了解代谢紊乱的发病机制和潜在治疗方法。