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

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...

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Veröffentlicht in:iScience 2022-07, Vol.25 (7), p.104603
Hauptverfasser: Inoue, Ryota, Tsuno, Takahiro, Togashi, Yu, Okuyama, Tomoko, Sato, Aoi, Nishiyama, Kuniyuki, Kyohara, Mayu, Li, Jinghe, Fukushima, Setsuko, Kin, Tatsuya, Miyashita, Daisuke, Shiba, Yusuke, Atobe, Yoshitoshi, Kiyonari, Hiroshi, Bando, Kana, Shapiro, A M James, Funakoshi, Kengo, Kulkarni, Rohit N, Terauchi, Yasuo, Shirakawa, Jun
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Sprache:eng
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Zusammenfassung: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.
ISSN:2589-0042