Age Related Insulin Resistance, Muscle, and Exercise Grant uri icon

abstract

  • Advancing age is typically accompanied by insulin resistance. This decrement is a significant public health problem as insulin resistance is a precipitating factor for cardiovascular disease (the #1 killer in the United States), type 2 diabetes, and hypertension. Relatively little, however, is known concerning the cellular mechanism(s) responsible for the insulin resistance of aging in humans, particularly in the primary target tissue for .insulin action, skeletal muscle. In a previous funding cycle, we observed that a small amount of the variance in the insulin resistance of human aging was accounted for by a reduced concentration of the insulin sensitive glucose transporter (GLUT4) in skeletal muscle; this finding suggests that another mechanism is involved. In the current proposal, the hypothesis to be tested is that the insulin sig!!a1leading to GLUT4 translocation is impaired with the aging process in human skeletal muscle, which subsequently contributes to insulin resistance. Our more specific working hypothesis is that insulin signal transduction is reduced in aged skeletal muscle at the level of Akt due to inhibition from increased muscle lipid content. This accumulation of muscle lipid may be due to a reduction in muscle oxidative capacity. As decrements during the aging process can be a consequence of physical inactivity, our secondary hypothesis is that the defect in insulin signal transduction with aging is compensated for with exercise training, possibly by increasing muscle oxidative capacity and/or reducing bioactive lipid stores. The following aims will test these hypotheses. Specific Aim 1. Determine if insulin signal transduction is impaired with in human skeletal muscle. Specific Aim 2. Determine if Iipid accumulation and/or impaired muscle oxidative capacity impedes insulin signal transduction in human skeletal muscle. capacity, reduce intramuscular lipid stores, and enhance insulin signal transduction? Specific Aim 3. activity in aged skeletal muscle.

date/time interval

  • September 2005 - June 2010