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Sirtuin 5 overexpression attenuates glucolipotoxicity-induced pancreatic β cells apoptosis and dysfunction.
- Source :
-
Experimental Cell Research . Oct2018, Vol. 371 Issue 1, p205-213. 9p. - Publication Year :
- 2018
-
Abstract
- Abstract Recently, SIRT5 was reported to be a predominant desuccinylase and demalonylase in mitochondria. Ablation of SIRT5 enhances the systemic succinylation and malonylation of mitochondrial proteins, including various metabolic enzymes; however, its function in pancreatic β cells has not yet been clarified. In this study, we evaluated the effects of SIRT5 overexpression on glucolipotoxicity-induced apoptosis in β cell lines. Full-length SIRT5, which preferentially targeted to mitochondria and partially to the nucleus and cytoplasm, was overexpressed in NIT-1 cells. Chronic exposure to excess palmitate and glucose (High-PA-G) induced apoptosis and suppressed glucose-stimulated insulin secretion in β cells. SIRT5 overexpression significantly alleviated apoptosis under the High-PA-G condition, accompanied by suppressed Caspase 3 activity and reduced malondialdehyde levels. SIRT5 overexpression also improved β cell secretory capacity in response to glucose under the High-PA-G condition, suggesting its protective role in β cell function. Furthermore, SIRT5 overexpression reversed the decreasing trend of anti-apoptotic factors BCL-2 and BCL-XL expression under High-PA-G condition. Further regulation mechanisms between SIRT5 and these anti-apoptotic factors remains to be explored in future studies. Our data reveal that SIRT5 is a potentially protective factor for pancreatic β cells against glucolipotoxicity-induced apoptosis and cell dysfunction. Highlights • SIRT5 expression significantly diminished in the pancreas of T2DM animals. • SIRT5 reduced apoptotic cell mass and retained glucose-stimulated insulin secretion in β cell lines upon glucolipotoxicity. • SIRT5 plays an essential role in maintaining the β cell mass and function under glucolipotoxicity condition. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SIRTUINS
*GENETIC overexpression
*PANCREATIC beta cells
*APOPTOSIS
*GLUCOSE
Subjects
Details
- Language :
- English
- ISSN :
- 00144827
- Volume :
- 371
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Experimental Cell Research
- Publication Type :
- Academic Journal
- Accession number :
- 131559962
- Full Text :
- https://doi.org/10.1016/j.yexcr.2018.08.011