The insulin signaling pathway activated downstream PI3K-AKT pathways, regulating processes such as glucose uptake, glycogen synthesis, and fatty acid synthesis.[48] Persistent activation of this pathway can stimulate the proliferation of colon cancer cells[49] and inhibit apoptosis.[50] The cGMP-PKG signaling pathway may influence the function of pancreatic beta cells, including insulin secretion and cell survival.[51] PKG, the central effector of cGMP, can inhibit tumor proliferation and angiogenesis through suppression of β-catenin/TCF and SOX9 signaling. This evidence concerns the gene HNF4A and colonic neoplasm.