INS and diabetes mellitus: In diabetes, the input of insulin signals to pancreatic β cells is decreased due to decreased insulin secretion caused by genetic predisposition, and the insulin signaling of pancreatic β cells is further impaired by lipids, adipokines, etc., resulting in decreased PI3K and MEK/Erk activity, increased apoptosis of pancreatic β cells, and impaired proliferation, resulting in decreased pancreatic β cell volume.