Age-associated alterations in cardiac and skeletal muscle glucose transporters, insulin and IGF-1 receptors, and PI3-kinase protein contents in the C57BL/6 mouse

Abstract

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 C57Bl/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 α 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 C57Bl/6 mouse.