Ca(2+) signaling and metabolic stress-induced pancreatic β-cell failure

Early in the development of Type 2 diabetes (T2D), metabolic stress brought on by insulin resistance and nutrient overload causes β-cell hyperstimulation. Herein we summarize recent studies that have explored the premise that an increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)), brought on by persistent metabolic stimulation of β-cells, causes β-cell dysfunction and failure by adversely affecting β-cell function, structure, and identity. This mini-review builds on several recent reviews that also describe how excess [Ca(2+)](i) impairs β-cell function.