Details

Autor(en) / Beteiligte

• Huang, Chien-Ning
• Li, Hsin-Hua
• Kornelius, Edy
• Yang, Yi Sun
• Ho, Hsiao-Li
• Bai, Yi-Chiao
• Kuo, Chien-Yin
• Peng, Chiung-Huei
• Lin, Chih-Li

Titel

2500-PUB: Mir-302 Protects against Glucolipotoxicity-Induced β-Cell Dysfunction and Apoptosis through the Regulation of MST1 and PDX1

Ist Teil von

• Diabetes (New York, N.Y.), 2019-06, Vol.68

Ort / Verlag

New York: American Diabetes Association

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Evidence is now revealed that the cytotoxic effect caused by elevated levels of plasma glucose and free fatty acids, also called as glucolipotoxicity, is particularly harmful for pancreatic β-cell. In fact, the mammalian Ste20-like kinase 1 (MST1) can mediate glucolipotoxicity-induced β-cell damages by degradation of pancreatic and duodenal homeobox 1 (PDX-1), which is known to play an essential role in maintaining β-cell function and survival. Interestingly, the activation of the pluripotency-related microRNA cluster miR-302 can protect β-cells from glucolipotoxicity-induced apoptosis. However, few studies have examined the related mechanism in detail. In the present study, we investigated the protective roles of miR-302 on rat pancreatic RINm5F β-cells, and demonstrated that MST1 was confirmed as a target of miR-302. As a result, the activation of miR-302restored the expression of PDX1 by inactivating MST1 thus ameliorating glucolipotoxicity-induced β-cell impairments. In addition, miR-302 also upregulated endogenous antioxidant signaling and autophagic activities during glucolipotoxicity, suggesting the anti-aging process may be also involved in miR-302-mediated protection. In conclusion, our study suggests that miR-302 may serve as a potential target for developing new diagnoses and therapies to reduce glucolipotoxicity in β-cells.