About Glipizide Second generation sulfonylurea, Pyrazine derivative, Medium-to-long acting Oral Antidiabetic Agent. Mechanism of Action of Glipizide It is a potent antidiabetic drug which exerts it`s action by increasing insulin release from the pancreas and by improving glucose tolerance. It acts on the "sulfonylurea receptors" on pancreatic ?-cell membrane and reduces conductance of ATP sensitive K+ channels and thus causes depolarization. This enhances Ca2+ influx and degranultion and thus increases insulin secretion rate at any glucose concentration. It primarily increases 2nd phase insulin secretion and has little effect on 1st phase. It also slows hepatic degradation of insulin and minor action of reducing glucagon release and increasing Somatostatin release. It also exerts extrapancreatic action- by sensitizing the target tissues such as liver to insulin action. It increases the number of insulin receptors and through a post receptor action improving translation of receptor a