IRS1 and hyperinsulinism: Hyperinsulinemia causes the activation of IGF-1 and insulin receptor substrate-1 (IRS-1), which further upregulate several signaling molecules, including p53, mitogen-activated protein kinase (MAPK) [89,90], and phosphatidylinositol-3 kinase (PI3K)/Akt [89,90], leading to cellular proliferation while also downregulating apoptosis [91].