Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and Ca2+ release from the ER

• DOI: 10.1016/j.isci.2022.104603
• Publication Date: 2022-06-14T17:24:59Z
• Authors: Ryota Inoue; Takahiro Tsuno; Yu Togashi; Tomoko Okuyama; Aoi Sato; Kuniyuki Nishiyama; Mayu Kyohara; Jinghe Li; Setsuko Fukushima; Tatsuya Kin; Daisuke Miyashita; Yusuke Shiba; Yoshitoshi Atobe; Hiroshi Kiyonari; Kana Bando; A.M. James Shapiro; Kengo Funakoshi; Rohit N. Kulkarni; Yasuo Terauchi; Jun Shirakawa
• Keywords: Pancreatic Islets

Uncoupling protein 2 (UCP2), a mitochondrial protein, is known to be upregulated in pancreatic islets of patients with type diabetes (T2DM); however, the pathological significance this increase UCP2 expression unclear. In study, we highlight molecular link between β-cells and β-cell failure by using genetically engineered mice human islets. β-cell-specific UCP2-overexpressing transgenic (βUCP2Tg) exhibited glucose intolerance reduction insulin secretion. Decreased function increased aldolase B (AldB) through oxidative-stress-mediated pathway were observed βUCP2Tg AldB, glycolytic enzyme, was associated reduced secretion via dysfunction impaired calcium release from endoplasmic reticulum (ER). Taken together, our findings provide new mechanism AldB. Targeting UCP2/AldB axis promising approach for recovery function.