Further, leucine has been demonstrated to have beneficial effects on glucose tolerance and insulin signaling when added to drinking water to a high-fat diet in mice [30], and chronic supplementation over 8 months prevented the development of overt diabetes in RCS10 mice, a polygenic mouse model of obesity and type 2 diabetes, and improved glucose-insulin homeostasis in yellow agouti (Ay) mice [31]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.