Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi, 110016, India.
Rev Endocr Metab Disord. 2021 Dec;22(4):973-986. doi: 10.1007/s11154-021-09652-2. Epub 2021 Apr 30.
The Akt isoforms-AS160-GLUT4 axis is the primary axis that governs glucose homeostasis in the body. The first step on the path to insulin resistance is deregulated Akt isoforms. This could be Akt isoform expression, its phosphorylation, or improper isoform-specific redistribution to the plasma membrane in a specific tissue system. The second step is deregulated AS160 expression, its phosphorylation, improper dissociation from glucose transporter storage vesicles (GSVs), or its inability to bind to 14-3-3 proteins, thus not allowing it to execute its function. The final step is improper GLUT4 translocation and aberrant glucose uptake. These processes lead to insulin resistance in a tissue-specific way affecting the whole-body glucose homeostasis, eventually progressing to an overt diabetic phenotype. Thus, the relationship between these three key proteins and their proper regulation comes out as the defining axis of insulin signaling and -resistance. This review summarizes the role of this central axis in insulin resistance and disease in a new light.
Akt 同工型-AS160-GLUT4 轴是调节体内葡萄糖稳态的主要轴。胰岛素抵抗发生的第一步是 Akt 同工型失调。这可能是 Akt 同工型的表达、磷酸化，或者同工型在特定组织系统中向质膜的异常特异性再分布。第二步是 AS160 表达失调、磷酸化、与葡萄糖转运体储存囊泡（GSVs）的异常解离，或者不能与 14-3-3 蛋白结合，从而无法发挥其功能。最后一步是 GLUT4 转运的异常和葡萄糖摄取的异常。这些过程以组织特异性的方式导致胰岛素抵抗，影响全身葡萄糖稳态，最终发展为明显的糖尿病表型。因此，这三种关键蛋白之间的关系及其适当的调节成为胰岛素信号转导和抵抗的决定性轴。本综述从新的角度总结了这一中心轴在胰岛素抵抗和疾病中的作用。
