Cell Biology Program, The Hospital for Sick Children, Toronto, Canada.
Department of Physiology, University of Toronto, Toronto, Canada.
J Clin Invest. 2021 Nov 1;131(21). doi: 10.1172/JCI154699.
Skeletal muscle preeminently determines whole-body glycemia. However, the molecular basis and inheritable influence that drive the progression of insulin resistance to type 2 diabetes remain debated. In this issue of the JCI, Haider and Lebastchi report on their use of induced pluripotent stem cell-derived (iPSC-derived) myoblasts (iMyos) to uncover multiple phosphoproteomic changes that carried over from the human to the cell-culture system. In this system devoid of in vivo influences, the researchers annotated changes between the sexes and between the most and least insulin-sensitive quintiles of a healthy population (defined by steady-state blood glucose levels). Many phosphoproteomic differences were detected in the absence of insulin, revealing that changes in the basal landscape of cells determine the efficiency of insulin action. Basal and insulin-dependent deficiencies of iPSCs and iMyos likely involve genetic and epigenetic determinants that modulate insulin sensitivity.
骨骼肌对全身血糖水平起决定作用。然而，导致胰岛素抵抗发展为 2 型糖尿病的分子基础和遗传影响仍存在争议。在本期 JCI 中，Haider 和 Lebastchi 报告了他们使用诱导多能干细胞衍生（iPSC 衍生）成肌细胞（iMyos）来揭示从人类到细胞培养系统的多个磷酸蛋白质组变化。在这个没有体内影响的系统中，研究人员注释了健康人群中两性之间和胰岛素敏感性最高和最低五分之一之间的变化（通过稳态血糖水平定义）。在没有胰岛素的情况下检测到许多磷酸蛋白质组差异，这表明细胞基础状态的变化决定了胰岛素作用的效率。iPSC 和 iMyos 的基础和胰岛素依赖性缺陷可能涉及调节胰岛素敏感性的遗传和表观遗传决定因素。
