SIRT6 protects against palmitate-induced pancreatic β-cell dysfunction and apoptosis.
Chronic exposure of pancreatic β-cells to abnormally elevated levels of free fatty acids can lead to β-cell dysfunction and even apoptosis, contributing to type 2 diabetes pathogenesis. In pancreatic β-cells, sirtuin 6 (SIRT6) has been shown to regulate insulin secretion in response to glucose stimulation. However, the roles played by SIRT6 in β-cells in response to lipotoxicity remain poorly understood. Our data indicated that SIRT6 protein and mRNA levels were reduced in islets from diabetic and aged mice. High concentrations of palmitate (PA) also led to a decrease in SIRT6 expression in MIN6 β-cells and resulted in cell dysfunction and apoptosis. Knockdown of Sirt6 caused an increase in cell apoptosis and impairment in insulin secretion in response to glucose in MIN6 cells even in the absence of PA exposure. Furthermore, overexpression of SIRT6 alleviated the palmitate-induced lipotoxicity with improved cell viability and increased glucose-stimulated insulin secretion. In summary, our data suggest that SIRT6 can protect against palmitate-induced β-cell dysfunction and apoptosis.
Department of Forensic MedicineXinxiang Medical University, Xinxiang, Henan, China xwxiong@xxmu.edu.cn xcdong@iu.edu.
Xiwen
X
Xiong
Department of Forensic MedicineXinxiang Medical University, Xinxiang, Henan, China.
Xupeng
X
Sun
Department of Forensic MedicineXinxiang Medical University, Xinxiang, Henan, China.
Qingzhi
Q
Wang
Department of Forensic MedicineXinxiang Medical University, Xinxiang, Henan, China.
Xinlai
X
Qian
Department of Biochemistry and Molecular BiologyIndiana University School of Medicine, Indianapolis, Indiana, USA.
Yang
Y
Zhang
Department of Biochemistry and Molecular BiologyIndiana University School of Medicine, Indianapolis, Indiana, USA.|Department of Endocrinology and MetabolismThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Xiaoyan
X
Pan
Department of Biochemistry and Molecular BiologyIndiana University School of Medicine, Indianapolis, Indiana, USA xwxiong@xxmu.edu.cn xcdong@iu.edu.
X Charlie
XC
Dong
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D016922:Cellular Senescence; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000009:adverse effects; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011994:Recombinant Proteins; D019308:Palmitic Acid; C501860:Sirt6 protein, mouse; D037761:Sirtuins
MIN6 cells; apoptosis; insulin secretion; palmitate; sirtuin 6