Objectives: 

It is well established that the hormonal decline associated with aging correlates with an increase in insulin resistance both in humans and in animal models. As a consequence of the insulin resistance there is impairment on glucose uptake in skeletal muscle and adipose tissue that leads to low intracellular energy levels. The AMP-activated protein kinase (AMPK) replies to high AMP/ATP intracellular ratios enhancing several molecular mechanisms that lead to increased insulin sensitivity, among them its activation causes an increase in the intracellular NAD+ levels that activates Sirt1. In turn mice models overexpressing Sirt1 had been reported to be protected from aging related phenotypes similar to type II diabetes.

Materials: 

For this propose virgin Wistar female rats at 8-10 weeks were ovariectomized. One week after ovariectomy, the animals were implanted subcutaneously in the posterior neck with 90-day-release 17beta-estradiol pellets (25 ug/pellet; Innovative Research of America, Sarasota, FL) or placebos containing no estradiol. The pellets were replaced every 90 days. Moreover intact rats were used as control group. Next, in order to test insulin sensitivity, every 6 months, 7 animals per group were anaesthetized and clamp experiments were performed. Blood samples before and after clamp experiments were collected from the jugular vein. Finally, samples of skeletal muscle were recovered and processed for western-blotting.

Results: 

In this work we assess the capability of a chronic treatment with a physiologic dose of 17beta-estradiol, to enhance kinases pathways in rat skeletal muscle that lead to an improvement of the insulin responding state and thus ameliorates one of the main symptoms of the aging-related metabolic syndrome.