INS and diabetes mellitus: Multiple animal models of diabetes have also demonstrated that the impaired insulin secretion characteristic of this disease, is due, in part, to dysfunctional Ca2+ oscillations,13-18 with studies on human β-cells corroborating this finding.19-21 These Ca2+ oscillations drive pulsatile insulin release22 – a secretory pattern that enhances hepatic insulin action,23 protects against insulin resistance,24 and is lost in T2DM.25-28 To understand how these Ca2+ oscillations become defective in T2DM, it is important to first understand how an islet generates and maintains these oscillations.