Ion Channels of the Islets in Type 2 Diabetes

Ca²⁺ is an essential signal for pancreatic β-cell function. Ca²⁺ plays critical roles in numerous β-cell pathways such as insulin secretion, transcription, metabolism, endoplasmic reticulum function, and the stress response. Therefore, β-cell Ca²⁺ handling is tightly controlled. At the plasma membrane, Ca²⁺ entry primarily occurs through voltage-dependent Ca²⁺ channels. Voltage-dependent Ca²⁺ channel activity is dependent on orchestrated fluctuations in the plasma membrane potential or voltage, which are mediated via the activity of many ion channels. During the pathogenesis of type 2 diabetes the β-cell is exposed to stressful conditions, which result in alterations of Ca²⁺ handling. Some of the changes in β-cell Ca²⁺ handling that occur under stress result from perturbations in ion channel activity, expression or localization. Defective Ca²⁺ signaling in the diabetic β-cell alters function, limits insulin secretion and exacerbates hyperglycemia. In this review, we focus on the β-cell ion channels that control Ca²⁺ handling and how they impact β-cell dysfunction in type 2 diabetes.