Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and Ca2+ release from the ER
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | iScience, Vol 25, Iss 7, Pp 104603- (2022) |
| Druh dokumentu: | article |
| ISSN: | 2589-0042 88027570 |
| DOI: | 10.1016/j.isci.2022.104603 |
| Popis: | Summary: Uncoupling protein 2 (UCP2), a mitochondrial protein, is known to be upregulated in pancreatic islets of patients with type 2 diabetes (T2DM); however, the pathological significance of this increase in UCP2 expression is unclear. In this study, we highlight the molecular link between the increase in UCP2 expression in β-cells and β-cell failure by using genetically engineered mice and human islets. β-cell-specific UCP2-overexpressing transgenic mice (βUCP2Tg) exhibited glucose intolerance and a reduction in insulin secretion. Decreased mitochondrial function and increased aldolase B (AldB) expression through oxidative-stress-mediated pathway were observed in βUCP2Tg islets. AldB, a glycolytic enzyme, was associated with reduced insulin secretion via mitochondrial dysfunction and impaired calcium release from the endoplasmic reticulum (ER). Taken together, our findings provide a new mechanism of β-cell dysfunction by UCP2 and AldB. Targeting the UCP2/AldB axis is a promising approach for the recovery of β-cell function. |
| Databáze: | Directory of Open Access Journals |
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