Garvan Institute of Medical Research, Darlinghurst Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2010, Australia.
Trends Endocrinol Metab. 2020 May;31(5):344-356. doi: 10.1016/j.tem.2020.01.016. Epub 2020 Feb 20.
The failure of insulin to suppress glucose production by the liver is a key aspect of the insulin resistance seen in type 2 diabetes. Lipid-activated protein kinase C epsilon has long been identified as an important mediator of diet-induced glucose intolerance and hepatic insulin resistance and the current view emphasizes a mechanism involving phosphorylation of the insulin receptor by the kinase to inhibit downstream insulin action. However, the significance of this direct effect in the liver has now been challenged by tissue-specific deletion of PKCε, which demonstrated a more prominent role for the kinase in adipose tissue to promote glucose intolerance. New insights regarding the role of PKCε therefore contribute to the understanding of indirect effects on hepatic glucose metabolism.
胰岛素抑制肝脏葡萄糖生成的失败是 2 型糖尿病中胰岛素抵抗的一个关键方面。脂激活蛋白激酶 C ɛ 长期以来一直被认为是饮食诱导的葡萄糖不耐受和肝胰岛素抵抗的重要介质，目前的观点强调了一种涉及激酶磷酸化胰岛素受体以抑制下游胰岛素作用的机制。然而，PKCɛ 的组织特异性缺失对这一直接作用在肝脏中的意义提出了挑战，该研究表明激酶在脂肪组织中发挥了更突出的作用，以促进葡萄糖不耐受。因此，关于 PKCɛ 作用的新见解有助于理解对肝葡萄糖代谢的间接影响。
