دورية أكاديمية
Sirtuin 6 regulates glucose-stimulated insulin secretion in mouse pancreatic beta cells
| العنوان: | Sirtuin 6 regulates glucose-stimulated insulin secretion in mouse pancreatic beta cells |
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| المؤلفون: | Xiong, Xiwen, Wang, Gaihong, Tao, Rongya, Wu, Pengfei, Kono, Tatsuyoshi, Li, Kevin, Ding, Wen-Xing, Tong, Xin, Tersey, Sarah A., Harris, Robert A., Mirmira, Raghavendra G., Evans-Molina, Carmella, Dong, X. Charlie |
| المساهمون: | Department of Biochemistry & Molecular Biology, IU School of Medicine |
| المصدر: | PMC |
| بيانات النشر: | Springer |
| سنة النشر: | 2016 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | Beta cell, Calcium, Glucose metabolism, Insulin secretion, Mitochondria, SIRT6 |
| الوصف: | AIMS/HYPOTHESIS: Sirtuin 6 (SIRT6) has been implicated in ageing, DNA repair and metabolism; however, its function in pancreatic beta cells is unclear. The aim of this study is to elucidate the role of SIRT6 in pancreatic beta cells. METHODS: To investigate the function of SIRT6 in pancreatic beta cells, we performed Sirt6 gene knockdown in MIN6 cells and generated pancreatic- and beta cell-specific Sirt6 knockout mice. Islet morphology and glucose-stimulated insulin secretion (GSIS) were analysed. Glycolysis and oxygen consumption rates in SIRT6-deficient beta cells were measured. Cytosolic calcium was monitored using the Fura-2-AM fluorescent probe (Invitrogen, Grand Island, NY, USA). Mitochondria were analysed by immunoblots and electron microscopy. RESULTS: Sirt6 knockdown in MIN6 beta cells led to a significant decrease in GSIS. Pancreatic beta cell Sirt6 knockout mice showed a ~50% decrease in GSIS. The knockout mouse islets had lower ATP levels compared with the wild-type controls. Mitochondrial oxygen consumption rates were significantly decreased in the SIRT6-deficient beta cells. Cytosolic calcium dynamics in response to glucose or potassium chloride were attenuated in the Sirt6 knockout islets. Numbers of damaged mitochondria were increased and mitochondrial complex levels were decreased in the SIRT6-deficient islets. CONCLUSIONS/INTERPRETATION: These data suggest that SIRT6 is important for GSIS from pancreatic beta cells and activation of SIRT6 may be useful to improve insulin secretion in diabetes. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Diabetologia; Xiong, X., Wang, G., Tao, R., Wu, P., Kono, T., Li, K., … Dong, X. C. (2016). Sirtuin 6 regulates glucose-stimulated insulin secretion in mouse pancreatic beta cells. Diabetologia, 59(1), 151–160. http://doi.org/10.1007/s00125-015-3778-2Test; https://hdl.handle.net/1805/12376Test |
| الإتاحة: | https://doi.org/10.1007/s00125-015-3778-2Test https://hdl.handle.net/1805/12376Test |
| حقوق: | Publisher Policy |
| رقم الانضمام: | edsbas.391D7A9A |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |