Ceddia R B, Somwar R, Maida A, Fang X, Bikopoulos G, Sweeney G
Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.
Diabetologia. 2005 Jan;48(1):132-9. doi: 10.1007/s00125-004-1609-y. Epub 2004 Dec 24.
AIMS/HYPOTHESIS: The aim of this study was to determine whether adiponectin elicits glucose uptake via increased GLUT4 translocation and to investigate the metabolic fate of glucose in skeletal muscle cells treated with globular adiponectin.
Basal and insulin-stimulated 2-deoxy-D: -[(3)H]glucose uptake, cell surface myc-tagged GLUT4 content, production of (14)CO(2) by oxidation of D: -[U-(14)C]glucose and [1-(14)C]oleate, and incorporation of D: -[U-(14)C]glucose into glycogen and lactate were measured in the presence and absence of globular adiponectin.
RT-PCR and Western blot analysis revealed that L6 cells and rat skeletal muscle cells express AdipoR1 mRNA and protein. Globular adiponectin increased both GLUT4 translocation and glucose uptake by increasing the transport V(max) of glucose without altering the K(m). Interestingly, the incorporation of D: -[U-(14)C]glucose into glycogen under basal and insulin-stimulated conditions was significantly decreased by globular adiponectin, whereas lactate production was increased. Furthermore, globular adiponectin did not affect glucose oxidation, but enhanced phosphorylation of AMP kinase and acetyl-CoA carboxylase, and fatty acid oxidation.
CONCLUSIONS/INTERPRETATION: The present study is the first to show that globular adiponectin increases glucose uptake in skeletal muscle cells via GLUT4 translocation and subsequently reduces the rate of glycogen synthesis and shifts glucose metabolism toward lactate production. These effects are consistent with the increased phosphorylation of AMP kinase and acetyl-CoA carboxylase and oxidation of fatty acids induced by globular adiponectin.
目的/假设：本研究旨在确定脂联素是否通过增加葡萄糖转运蛋白4（GLUT4）转位来促进葡萄糖摄取，并研究球状脂联素处理的骨骼肌细胞中葡萄糖的代谢去向。
在存在和不存在球状脂联素的情况下，测量基础状态和胰岛素刺激下的2-脱氧-D：-[(3)H]葡萄糖摄取、细胞表面带有myc标签的GLUT4含量、D：-[U-(14)C]葡萄糖和[1-(14)C]油酸氧化产生的(14)CO(2)，以及D：-[U-(14)C]葡萄糖掺入糖原和乳酸的情况。
逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹分析显示，L6细胞和大鼠骨骼肌细胞表达脂联素受体1（AdipoR1）的信使核糖核酸（mRNA）和蛋白质。球状脂联素通过增加葡萄糖的转运最大速度（V(max)）而不改变米氏常数（K(m)），从而增加GLUT4转位和葡萄糖摄取。有趣的是，在基础状态和胰岛素刺激条件下，球状脂联素显著降低了D：-[U-(14)C]葡萄糖掺入糖原的量，而乳酸生成增加。此外，球状脂联素不影响葡萄糖氧化，但增强了腺苷酸活化蛋白激酶（AMP激酶）和乙酰辅酶A羧化酶的磷酸化，并促进脂肪酸氧化。
结论/解读：本研究首次表明，球状脂联素通过GLUT4转位增加骨骼肌细胞中的葡萄糖摄取，随后降低糖原合成速率，并使葡萄糖代谢转向乳酸生成。这些作用与球状脂联素诱导的AMP激酶和乙酰辅酶A羧化酶磷酸化增加以及脂肪酸氧化一致。
