TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet.

Mitochondrial Ca ([Ca]) homeostasis is critical for β-cell function and becomes disrupted during the pathogenesis of diabetes. [Ca] uptake is dependent on elevations in cytoplasmic Ca ([Ca]) and endoplasmic reticulum Ca ([Ca]) release, both of which are regulated by the two-pore domain K channel TALK-1. Here, utilizing a novel β-cell TALK-1-knockout (β-TALK-1-KO) mouse model, we found that TALK-1 limited β-cell [Ca] accumulation and ATP production.