Our previous study has shown that systemic deletion of SH2B1 in generation of SH2B1-deficient mice inhibited the activation of PI3K/Akt and Erk1/2 pathways to develop age-dependent hyperinsulinemia, hyperglycemia and glucose intolerance [22], suggesting that SH2B1 is an upstream regulatory of PI3K/Akt signaling in endocrine disease. The gene discussed is MAPK3; the disease is hyperinsulinism.