INS and Hyperglycemia: T2DM is caused by two mechanisms: (1) glucose, a main metabolic fuel produced in the liver through the gluconeogenesis pathway during fasting when insulin is downregulated, is a key contributor to hyperglycemia; (2) reduced insulin-mediated glucose absorption and resultant diabetic organ damage are caused by insulin resistance in peripheral target tissues and altered insulin secretory capacity of pancreatic β-cells [56].