SIRT6 protects against palmitateinduced pancreatic β-cell dysfunction and apoptosis

Xiwen Xiong, Xupeng Sun, Qingzhi Wang, Xinlai Qian, Yang Zhang, Xiaoyan Pan, X. Dong

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)159-165
Number of pages7
JournalJournal of Endocrinology
Volume231
Issue number2
DOIs
StatePublished - 2016

Fingerprint

Apoptosis
Palmitates
Insulin
Glucose
Nonesterified Fatty Acids
Type 2 Diabetes Mellitus
Cell Survival
Messenger RNA
Proteins

Keywords

  • Apoptosis
  • Insulin secretion
  • mIN6 cells
  • Palmitate
  • Sirtuin 6

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

SIRT6 protects against palmitateinduced pancreatic β-cell dysfunction and apoptosis. / Xiong, Xiwen; Sun, Xupeng; Wang, Qingzhi; Qian, Xinlai; Zhang, Yang; Pan, Xiaoyan; Dong, X.

In: Journal of Endocrinology, Vol. 231, No. 2, 2016, p. 159-165.

Research output: Contribution to journalArticle

Xiong, Xiwen ; Sun, Xupeng ; Wang, Qingzhi ; Qian, Xinlai ; Zhang, Yang ; Pan, Xiaoyan ; Dong, X. / SIRT6 protects against palmitateinduced pancreatic β-cell dysfunction and apoptosis. In: Journal of Endocrinology. 2016 ; Vol. 231, No. 2. pp. 159-165.
@article{0b35d37eeadf46d4afe288bfd3303284,
title = "SIRT6 protects against palmitateinduced pancreatic β-cell dysfunction and apoptosis",
abstract = "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.",
keywords = "Apoptosis, Insulin secretion, mIN6 cells, Palmitate, Sirtuin 6",
author = "Xiwen Xiong and Xupeng Sun and Qingzhi Wang and Xinlai Qian and Yang Zhang and Xiaoyan Pan and X. Dong",
year = "2016",
doi = "10.1530/JOE-16-0317",
language = "English (US)",
volume = "231",
pages = "159--165",
journal = "Journal of Endocrinology",
issn = "0022-0795",
publisher = "Society for Endocrinology",
number = "2",

}

TY - JOUR

T1 - SIRT6 protects against palmitateinduced pancreatic β-cell dysfunction and apoptosis

AU - Xiong, Xiwen

AU - Sun, Xupeng

AU - Wang, Qingzhi

AU - Qian, Xinlai

AU - Zhang, Yang

AU - Pan, Xiaoyan

AU - Dong, X.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Insulin secretion

KW - mIN6 cells

KW - Palmitate

KW - Sirtuin 6

UR - http://www.scopus.com/inward/record.url?scp=85005950885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85005950885&partnerID=8YFLogxK

U2 - 10.1530/JOE-16-0317

DO - 10.1530/JOE-16-0317

M3 - Article

VL - 231

SP - 159

EP - 165

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 2

ER -