title: Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 reduces pancreatic β-cells apoptosis in glucotoxicity through activation of autophagy.
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.
authors.affiliation: 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: 1784541388@qq.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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: chenke520@yeah.net.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: 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: linghaowang@126.com.
authors.forename: Linghao
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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: daynstars@gmail.com.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Wan
authors.affiliation: 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: sangdelama@gmail.com.
authors.forename: Chandrama
authors.initials: C
authors.lastname: Shrestha
authors.affiliation: Department of Physiology, Kansas City University of Medicine and Biosciences, 1750 Independence Ave, Kansas City, MO 64106, USA. Electronic address: jzhou@kcumb.edu.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 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: easd04mzh@126.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Mo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D005947:Glucose / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017208:Rats, Wistar; D000099202:PTEN-Induced Putative Kinase
chemical_list: D005947:Glucose; D051059:PTEN Phosphohydrolase; D011494:Protein Kinases; D034741:RNA, Small Interfering; D000099202:PTEN-Induced Putative Kinase; C487216:Pten protein, rat
keywords: Apoptosis; Autophagy; High glucose; Phosphatase and tensin homologue (PTEN)-induced putative kinase 1; β-cells