INS and Hyperglycemia: This indicates that overexpression of SHIP2 in liver leads to systemic insulin resistance.131 Adenovirus‐mediated overexpression of 5′‐phosphatase‐defective SHIP2 (dominant‐negative SHIP2) in diabetic db/db mice improved the ability of insulin to induce Akt activation in the liver, and partly reduced the enhanced expression of gluconeogenic genes.131 This lowered fasting blood glucose and reduced elevated glucose and insulin levels after oral glucose intake, indicating that inhibition of SHIP2 in liver is effective in ameliorating hyperglycemia.