School of Medical Sciences, Faculty of Medicine, UNSW Sydney, Australia.
Sci Rep. 2019 Feb 4;9(1):1350. doi: 10.1038/s41598-018-38014-3.
Therapeutic interventions that increase plasma high density lipoprotein (HDL) and apolipoprotein (apo) A-I levels have been reported to reduce plasma glucose levels and attenuate insulin resistance. The present study asks if this is a direct effect of increased glucose uptake by skeletal muscle. Incubation of primary human skeletal muscle cells (HSKMCs) with apoA-I increased insulin-dependent and insulin-independent glucose uptake in a time- and concentration-dependent manner. The increased glucose uptake was accompanied by enhanced phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), the serine/threonine kinase Akt and Akt substrate of 160 kDa (AS160). Cell surface levels of the glucose transporter type 4, GLUT4, were also increased. The apoA-I-mediated increase in glucose uptake by HSKMCs was dependent on phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt, the ATP binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-B1). Taken together, these results establish that apoA-I increases glucose disposal in skeletal muscle by activating the IR/IRS-1/PI3K/Akt/AS160 signal transduction pathway. The findings suggest that therapeutic agents that increase apoA-I levels may improve glycemic control in people with type 2 diabetes.
研究表明，增加血浆高密度脂蛋白（HDL）和载脂蛋白（apo）A-I 水平的治疗干预措施可降低血浆葡萄糖水平并减轻胰岛素抵抗。本研究旨在探讨这是否是骨骼肌葡萄糖摄取增加的直接作用。用 apoA-I 孵育原代人骨骼肌细胞（HSKMC）可使胰岛素依赖性和胰岛素非依赖性葡萄糖摄取呈时间和浓度依赖性增加。葡萄糖摄取的增加伴随着胰岛素受体（IR）、胰岛素受体底物-1（IRS-1）、丝氨酸/苏氨酸激酶 Akt 和 Akt 底物 160kDa（AS160）的磷酸化增强。葡萄糖转运蛋白 4（GLUT4）的细胞表面水平也增加了。apoA-I 介导的 HSKMC 葡萄糖摄取增加依赖于磷脂酰肌醇-4,5-二磷酸 3-激酶（PI3K）/Akt、ATP 结合盒转运蛋白 A1（ABCA1）和清道夫受体 B 型 I（SR-B1）。综上所述，这些结果表明 apoA-I 通过激活 IR/IRS-1/PI3K/Akt/AS160 信号转导通路增加骨骼肌中的葡萄糖摄取。这些发现表明，增加 apoA-I 水平的治疗药物可能改善 2 型糖尿病患者的血糖控制。
