In K/KAy mice with genetic obesity-associated insulin resistance that exhibit elevated phosphorylation levels of ser307 and ser636/639 of IRS-1, inhibition/deletion of raptor, a regulatory-associated protein of mTOR, resulted in improved glucose tolerance, suppressed ser307 and ser636/639 phosphorylation of IRS-1 and restored the insulin-induced PI3K activation and Akt phosphorylation in hepatic tissues [65]. Here, IRS1 is linked to obesity due to melanocortin 4 receptor deficiency.