Lewis Gary F, Carpentier Andre C, Pereira Sandra, Hahn Margaret, Giacca Adria
Departments of Medicine and Physiology, University of Toronto, Toronto, ON, Canada; Banting & Best Diabetes Centre, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Division of Endocrinology, Department of Medicine, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC, Canada.
Cell Metab. 2021 Apr 6;33(4):709-720. doi: 10.1016/j.cmet.2021.03.007. Epub 2021 Mar 24.
There is general agreement that the acute suppression of hepatic glucose production by insulin is mediated by both a direct and an indirect effect on the liver. There is, however, no consensus regarding the relative magnitude of these effects under physiological conditions. Extensive research over the past three decades in humans and animal models has provided discordant results between these two modes of insulin action. Here, we review the field to make the case that physiologically direct hepatic insulin action dominates acute suppression of glucose production, but that there is also a delayed, second order regulation of this process via extrahepatic effects. We further provide our views regarding the timing, dominance, and physiological relevance of these effects and discuss novel concepts regarding insulin regulation of adipose tissue fatty acid metabolism and central nervous system (CNS) signaling to the liver, as regulators of insulin's extrahepatic effects on glucose production.
人们普遍认为，胰岛素对肝脏葡萄糖生成的急性抑制作用是通过对肝脏的直接和间接作用介导的。然而，在生理条件下，这些作用的相对大小尚无共识。过去三十年在人类和动物模型上进行的广泛研究，在这两种胰岛素作用模式之间得出了不一致的结果。在这里，我们回顾该领域的研究情况，以论证在生理状态下，肝脏胰岛素的直接作用在急性抑制葡萄糖生成中占主导地位，但该过程也通过肝外作用存在延迟的二阶调节。我们还就这些作用的时间、主导性和生理相关性发表了看法，并讨论了关于胰岛素调节脂肪组织脂肪酸代谢以及中枢神经系统（CNS）向肝脏发出信号的新概念，这些是胰岛素肝外作用调节葡萄糖生成的调节器。
