Insulin resistance and beta cell dysfunction are leading components in the pathogenesis of type 2 diabetes mellitus. Over-nutrition leads to activation of the mTOR/S6K1. S6K1 activation leads to serine phosphorylation of IRS1, triggering its proteosomal degradation and interfering with insulin metabolic signaling. We investigated the role of over-nutrition on S6K1 pathway, oxidative stress and insulin signaling in the Zucker Obese (ZO) rat, which displays severe obesity, systemic insulin resistance, glucose intolerance, and hypertension
