Resistance to the hypoglycemic action of insulin develops within 7 days of bedrest in young,
healthy volunteers. We propose that the same event occurs in elderly individuals confined to
bed, that alterations in lipid metabolism are, at least in part, responsible for the insulin
resistance associated with bedrest, and that the accumulation of intracellular triglyceride
(TG) in liver and muscle will play a role in impairing insulin action. Further, we propose
that the PPARĪ± (Peroxisome Proliferator-Activated Receptor Alpha) agonist fenofibrate will
increase tissue fatty acid disposal by activating mitochondrial oxidative capacity, thereby
improving insulin sensitivity.
We will investigate a series of specific hypotheses designed to examine the role of altered
lipid metabolism in the development of insulin-resistance associated with bedrest. Further,
since inactivity is likely a principal factor in the development of insulin resistance in the
elderly, the response to the inactivity imposed by bedrest represents an acceleration of the
normal development of insulin resistance in elderly individuals. Therefore, the results of
this study will also be pertinent to the understanding of the mechanisms responsible for the
natural development of insulin resistance in free-living elderly.