INSULIN SENSITIVITY AND INTRACELLULAR SIGNALING OF MUSCLE PROTEIN SYNTHESIS IN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: The development of insulin resistance is a common feature of aging. Loss of muscle mass and strength with aging is also an increasingly common problem. There is evidence that elderly muscle does not respond to insulin in the same manner as young muscle. The purpose of this study is to determine the response of muscle tissue to insulin and resistive exercise in the elderly. Hypothesis: We hypothesize that insulin resistance in the elderly contributes to loss of muscle mass. We also hypothesize that resistance exercise improves the loss of muscle in the elderly. Specific Aims and Procedures (summary): 1. To determine the factors associated with changes in muscle protein synthesis in the elderly in response to insulin and resistive exercise. 2. To determine the time course of the response of the muscle tissue to the resistive exercise, insulin and, the combination of insulin and resistive exercise. The data from this pilot study will be used in planning a larger trial investigating the relationship between insulin resistance and muscle loss in the elderly. Experimental Design (summary): This study will include normal healthy elderly between the ages of 60-85 who do not participate in any form of resistive exercise. Subjects will undergo a comprehensive screening visit prior to participating in the study. Subjects will be randomly selected (for example, by the flip of a coin), to participate in one of three studies. Study 1 will involve a period of rest followed by infusion of insulin for 6 hours into a femoral artery. Study 2 will involve a resistance exercise workout of the legs (i.e. four different leg exercises), followed by an 8-hour insulin infusion period. Study 3 will involve the same resistance exercise workout as Study 2 but will be followed by 8 hours of rest with no insulin infusion. Significance (summary): Identification of the cells responsible for defects in muscle metabolism that lead to muscle loss and aging will provide the information needed for development of effective therapies to treat sarcopenia.