Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 reduces pancreatic β-cells apoptosis in glucotoxicity through activation of autophagy

Chronic elevated glucose is harmful to pancreatic β-cells, resulting in pancreatic β-cells dysfunction and apoptosis. Understanding the molecular mechanisms associated with β-cells survival is pivotal for the prevention of β-cells injury caused by glucotoxicity. The role of Phosphatase and tensin ho...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2016-08, Vol.476 (4), p.299-305
Main Authors: Zhang, Juan, Chen, Ke, Wang, Linghao, Wan, Xinxin, Shrestha, Chandrama, Zhou, Jingsong, Mo, Zhaohui
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Autophagy
Glucose - metabolism
High glucose
Insulin-Secreting Cells - cytology
Insulin-Secreting Cells - metabolism
Male
Phosphatase and tensin homologue (PTEN)-induced putative kinase 1
Protein Kinases - genetics
Protein Kinases - metabolism
PTEN Phosphohydrolase - metabolism
Rats, Wistar
RNA Interference
RNA, Small Interfering - genetics
β-cells
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Summary:Chronic elevated glucose is harmful to pancreatic β-cells, resulting in pancreatic β-cells dysfunction and apoptosis. Understanding the molecular mechanisms associated with β-cells survival is pivotal for the prevention of β-cells injury caused by glucotoxicity. The role of Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1) in the fate of pancreatic β-cells constantly exposed to high glucose was studied. Sustained high glucose increased PINK1 protein expression both in rat pancreatic β-cells and INS-1 β-cells, and that this increase can be inhibited by PINK1 knockdown and further enhanced by PINK1 over-expression. PINK1 deficiency aggravated glucotoxicity-induced pancreatic β-cells apoptosis and inhibition of autophagy whereas PINK1 could reverse these adverse effects. This study provides fundamental data supporting the potential protective role of PINK1 as a new therapeutic target necessary to preserve β-cells survival under non-physiological hyperglycemia conditions. •PINK1 is induced by surplus high glucose in pancreatic β-cells.•PINK1 protects pancreatic β-cells against surplus high glucose toxicity.•PINK1 most likely evokes autophagy to protect pancreatic β-cells.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.05.116