| First Author | Graff SM | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 1 | Pages | 113673 |
| PubMed ID | 38206814 | Mgi Jnum | J:344958 |
| Mgi Id | MGI:7578702 | Doi | 10.1016/j.celrep.2024.113673 |
| Citation | Graff SM, et al. (2024) TALK-1-mediated alterations of beta-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet. Cell Rep 43(1):113673 |
| abstractText | Mitochondrial Ca(2+) ([Ca(2+)](m)) homeostasis is critical for beta-cell function and becomes disrupted during the pathogenesis of diabetes. [Ca(2+)](m) uptake is dependent on elevations in cytoplasmic Ca(2+) ([Ca(2+)](c)) and endoplasmic reticulum Ca(2+) ([Ca(2+)](ER)) release, both of which are regulated by the two-pore domain K(+) channel TALK-1. Here, utilizing a novel beta-cell TALK-1-knockout (beta-TALK-1-KO) mouse model, we found that TALK-1 limited beta-cell [Ca(2+)](m) accumulation and ATP production. However, following exposure to a high-fat diet (HFD), ATP-linked respiration, glucose-stimulated oxygen consumption rate, and glucose-stimulated insulin secretion (GSIS) were increased in control but not TALK1-KO mice. Although beta-TALK-1-KO animals showed similar GSIS before and after HFD treatment, these mice were protected from HFD-induced glucose intolerance. Collectively, these data identify that TALK-1 channel control of beta-cell function reduces [Ca(2+)](m) and suggest that metabolic remodeling in diabetes drives dysglycemia. |
