Blocking Ca2+ Channel β3 Subunit Reverses Diabetes

• DOI: 10.1016/j.celrep.2018.06.086
• Publication Date: 2018-07-24T17:14:57Z
• Authors: Kayoung Lee; Jaeyoon Kim; Martin Köhler; Jia Yu; Yue Shi; Shao-Nian Yang; Sung Ho Ryu; Per-Olof Berggren
• Keywords: Blocking (statistics)

Voltage-gated Ca2+ channels (Cav) are essential for pancreatic beta cell function as they mediate influx, which leads to insulin exocytosis. The β3 subunit of Cav (Cavβ3) has been suggested regulate cytosolic ([Ca2+]i) oscillation frequency and secretion under physiological conditions, but its role in diabetes is unclear. Here, we report that islets from diabetic mice show Cavβ3 overexpression, altered [Ca2+]i dynamics, impaired upon glucose stimulation. Consequently, high-fat diet (HFD)-induced diabetes, Cavβ3-deficient (Cavβ3−/−) showed improved islet enhanced tolerance. Normalization expression ob/ob by an antisense oligonucleotide rescued the dynamics secretion. Importantly, transplantation Cavβ3−/− into anterior chamber eye tolerance HFD-fed mice. overexpression human also We thus suggest may serve a druggable target treatment.