Comparably, transgenic mice expressing a dominant-negative form of SHP2 showed insulin resistance in muscle and adipocytes (Maegawa et al., 1999), whereas tissue-specific reduction of SHP2 function in hepatocytes or adipocytes showed increased tolerance to insulin and high-fat diets (Matsuo et al., 2010; Nagata et al., 2012). This evidence concerns the gene PTPN11 and Insulin resistance.