Martineau L C, Chadan S G, Parkhouse W S
Metabolic Biochemistry Laboratory, Faculty of Applied Science, Simon Fraser University, Burnaby, BC, Canada.
Mech Ageing Dev. 1999 Jan 15;106(3):217-32. doi: 10.1016/s0047-6374(98)00106-7.
We investigated potential age-related changes in cardiac and skeletal muscle protein contents of glut-4 and glut-1 transporters, insulin and insulin-like growth factor-1 (IGF-1) receptors, and phosphatidylinositol 3-kinase (PI3-kinase) in the C57B1/6 mouse. Myocardial glut-4 content increased four- to five-fold between mid- to late-adulthood with no further age-related changes. Increases in myocardial glut-1 preceded the increase in glut-4 and was of a much smaller magnitude (25-40%). Skeletal muscle glut-4 was also increased (38-49%) and no further changes were noted between adulthood and old age. Cardiac insulin receptor and the p85 alpha subunit of PI3-kinase both declined by about 40%, whereas the skeletal muscle content of these two proteins were unaffected by aging. Cardiac (-23 to -24%) and skeletal muscle (-40 to -62%) IGF-1 receptor levels were decreased in adult and old animals with senescence being associated with a further decrease in cardiac IGF-1 receptor levels to 20% of controls. A two- to three-fold increase in both basal and maximal in vitro autophosphorylation of the cardiac insulin and IGF-1 receptors by their respective ligands was observed with senescence. It appears that cardiac and skeletal muscle demonstrate differential responses in terms of the magnitude and temporal responses of age-associated alterations in glucose transport related protein contents in the C57B1/6 mouse.
我们研究了C57B1/6小鼠心脏和骨骼肌中葡萄糖转运蛋白4(glut-4)和葡萄糖转运蛋白1(glut-1)、胰岛素及胰岛素样生长因子-1(IGF-1)受体以及磷脂酰肌醇3激酶(PI3-激酶)的蛋白质含量与年龄相关的潜在变化。成年中期到成年晚期,心肌中glut-4含量增加了4至5倍,且未观察到与年龄相关的进一步变化。心肌中glut-1的增加先于glut-4,且增加幅度小得多(25%-40%)。骨骼肌中glut-4也增加了(38%-49%),成年期到老年期未观察到进一步变化。心脏胰岛素受体和PI3-激酶的p85α亚基均下降了约40%,而这两种蛋白质在骨骼肌中的含量不受衰老影响。成年和老年动物心脏(-23%至-24%)和骨骼肌(-40%至-62%)的IGF-1受体水平降低,衰老与心脏IGF-1受体水平进一步降至对照组的20%相关。衰老过程中观察到,心脏胰岛素和IGF-1受体被各自配体进行的基础和最大体外自磷酸化均增加了2至3倍。在C57B1/6小鼠中,心脏和骨骼肌在与年龄相关的葡萄糖转运相关蛋白质含量变化的幅度和时间反应方面表现出不同的反应。