This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Objective: Aging is associated with an increase in insulin resistance that may be affected more by obesity and physical inactivity than age per se. Insulin resistance is an underlying abnormality in various metabolic disorders such as type 2 diabetes, hyperlipidemia, and hypertension; metabolic diseases that increase cardiovascular morbidity and mortality with aging. Numerous studies show that moderate weight loss (WL) plus aerobic exercise (AEX) improve glucose tolerance and insulin sensitivity in older individuals. However, the molecular and cellular mechanisms underlying these metabolic changes with WL+AEX are not certain. Hypothesis/Design: It is our hypothesis that a lifestyle intervention that incorporates a moderate rate of WL (250-350 kcal/day deficit) plus AEX (70-75% heart rate reserve) will improve glucose tolerance and glucose utilization (80 mU/m2/min hyperinsulinemic-euglycemic clamp) in overweight (25-35 kg/m2 body mass index), older (60-75 y) glucose intolerant men and women through cellular mechanisms that involve increases in the content, phosphorylation, or activity of intermediates of the insulin-signaling cascade in skeletal muscle.
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