INS and diabetes mellitus: Specially, loss of function of NKX6.1 resulted in dysfunction in insulin synthesis and secretion, leading to diabetes as a consequence [63].Of note, over-expression of PAX4 (paired box gene 4, also known as MODY9) increased the number of insulin-secreting pancreatic β cells [64], cells that generate only one hormone (insulin), by suppressing the expression of glucagon-secreting cells [65].