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

Juan Zhang; Ke Chen; Linghao Wang; Xinxin Wan; Chandrama Shrestha; Jingsong Zhou; Zhaohui Mo

doi:10.1016/j.bbrc.2016.05.116

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

Biochem Biophys Res Commun. 2016 Aug 5;476(4):299-305. doi: 10.1016/j.bbrc.2016.05.116. Epub 2016 May 24.

Authors

Juan Zhang¹, Ke Chen², Linghao Wang³, Xinxin Wan⁴, Chandrama Shrestha⁵, Jingsong Zhou⁶, Zhaohui Mo⁷

Affiliations

¹ Department of Endocrinology and Metabolism, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. Electronic address: [email protected].
² Department of Endocrinology and Metabolism, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. Electronic address: [email protected].
³ Department of Endocrinology and Metabolism, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. Electronic address: [email protected].
⁴ Department of Endocrinology and Metabolism, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. Electronic address: [email protected].
⁵ Department of Endocrinology and Metabolism, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. Electronic address: [email protected].
⁶ Department of Physiology, Kansas City University of Medicine and Biosciences, 1750 Independence Ave, Kansas City, MO 64106, USA. Electronic address: [email protected].
⁷ Department of Endocrinology and Metabolism, The Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, PR China. Electronic address: [email protected].

PMID: 27233610
DOI: 10.1016/j.bbrc.2016.05.116

Abstract

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.

Keywords: Apoptosis; Autophagy; High glucose; Phosphatase and tensin homologue (PTEN)-induced putative kinase 1; β-cells.

MeSH terms

Animals
Apoptosis*
Autophagy*
Glucose / metabolism*
Insulin-Secreting Cells / cytology
Insulin-Secreting Cells / metabolism*
Male
PTEN Phosphohydrolase / metabolism
Protein Kinases / genetics
Protein Kinases / metabolism*
RNA Interference
RNA, Small Interfering / genetics
Rats, Wistar

Substances

RNA, Small Interfering
Protein Kinases
PTEN-induced putative kinase
PTEN Phosphohydrolase
Pten protein, rat
Glucose