Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, Li Ka Shing Institute of Health, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, N.T., Hong Kong, China.
Cell Signal. 2010 Oct;22(10):1513-22. doi: 10.1016/j.cellsig.2010.05.020. Epub 2010 Jun 4.
Insulin and AMP-activated protein kinase (AMPK) signal pathways are involved in the regulation of glucose uptake. The integration of signals between these two pathways to maintain glucose homeostasis remains elusive. In this work, stimulation of insulin and berberine conferred a glucose uptake or surface glucose transporter 4 (GLUT4) translocation that was less than simple summation of their effects in insulin-sensitive muscle cells. Using specific inhibitors to key kinases of both pathways and PKCzeta small interference RNA, protein kinase C zeta (PKCzeta) was found to regulate insulin-stimulated protein kinase B (PKB) activation and inhibit AMPK activity on dorsal cell surface. In the presence of berberine, PKCzeta controlled AMPK activation and AMPK blocked PKB activity in perinuclear region. The inhibition effect of PKCzeta on AMPK activation or the arrestment of PKB activity by AMPK still existed in basal condition. These results suggest that there is antagonistic regulation between insulin and AMPK signal pathways, which is mediated by the switch roles of PKCzeta.
胰岛素和 AMP 激活的蛋白激酶（AMPK）信号通路参与葡萄糖摄取的调节。这两条通路之间的信号整合以维持葡萄糖内稳态仍然难以捉摸。在这项工作中，胰岛素和小檗碱的刺激赋予了葡萄糖摄取或表面葡萄糖转运蛋白 4（GLUT4）易位，其效果小于胰岛素敏感肌肉细胞中它们的简单总和。使用两条通路的关键激酶的特异性抑制剂和 PKCzeta 小干扰 RNA，发现蛋白激酶 C zeta（PKCzeta）调节胰岛素刺激的蛋白激酶 B（PKB）激活，并抑制背侧细胞表面的 AMPK 活性。在小檗碱存在的情况下，PKCzeta 控制 AMPK 激活，而 AMPK 在核周区域阻止 PKB 活性。PKCzeta 对 AMPK 激活的抑制作用或 AMPK 对 PKB 活性的阻滞在基础条件下仍然存在。这些结果表明，胰岛素和 AMPK 信号通路之间存在拮抗调节，这是由 PKCzeta 的开关作用介导的。
