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Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway

INTRODUCTION: Blood glucose fluctuation is an important factor for the development of diabetic complications. Glucose fluctuation aggravated the renal injury in diabetic nephropathy. In the present study, our aim was to investigate the effects of blood glucose fluctuation on the glomerular mesangal...

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Autores principales: Ying, Changjiang, Wang, Shanshan, Lu, Yan, Chen, Lei, Mao, Yizhen, Ling, Hongwei, Cheng, Xingbo, Zhou, Xiaoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524177/
https://www.ncbi.nlm.nih.gov/pubmed/31110541
http://dx.doi.org/10.5114/aoms.2019.84739
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author Ying, Changjiang
Wang, Shanshan
Lu, Yan
Chen, Lei
Mao, Yizhen
Ling, Hongwei
Cheng, Xingbo
Zhou, Xiaoyan
author_facet Ying, Changjiang
Wang, Shanshan
Lu, Yan
Chen, Lei
Mao, Yizhen
Ling, Hongwei
Cheng, Xingbo
Zhou, Xiaoyan
author_sort Ying, Changjiang
collection PubMed
description INTRODUCTION: Blood glucose fluctuation is an important factor for the development of diabetic complications. Glucose fluctuation aggravated the renal injury in diabetic nephropathy. In the present study, our aim was to investigate the effects of blood glucose fluctuation on the glomerular mesangal cells and its related mechanism. MATERIAL AND METHODS: Mesangial cells were divided into four groups: the normal glucose group (NG) cells were incubated in normal glucose conditions (5.6 mmol/l); the high glucose group (HG) cells were treated with 25 mmol/l; the glucose fluctuation (FG) group received 5.6 mmol/l and 25 mmol/l glucose repeated 3 times; the mannitol group (MG) received 5.6 mmol/l glucose plus 24.4 mmol/l mannitol as a control. Cell viability and apoptosis were detected, reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels were measured. Phosphorylated ser/thr protein kinase (P-AKT, phosphor-Ser473), phosphorylated glycogen synthase kinase-3β (P-GSK-3β, phosphor-Ser9) and cleaved cysteinyl aspartate-specific proteinase-3 (cleaved caspase-3) levels were assessed using western blot. RESULTS: Data suggested that mesangial cells in the FG group show higher cell viability in 12 h, and lower cell viability from 48 h. The FG group showed cell apoptosis accompanied by a significant MDA level increase and SOD activity decrease in 48 h. More importantly, glucose fluctuation could aggravate oxidative stress in glomerular mesangial cells. Furthermore, the P-AKT level was lower, and increased P-GSK-3β and cleaved caspase-3 levels were higher in the FG group than in the HG group. CONCLUSIONS: Glucose fluctuation aggravates mesangial cell apoptosis, which may be partly induced by activating oxidative stress and inhibiting the AKT signaling pathway.
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spelling pubmed-65241772019-05-20 Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway Ying, Changjiang Wang, Shanshan Lu, Yan Chen, Lei Mao, Yizhen Ling, Hongwei Cheng, Xingbo Zhou, Xiaoyan Arch Med Sci Basic Research INTRODUCTION: Blood glucose fluctuation is an important factor for the development of diabetic complications. Glucose fluctuation aggravated the renal injury in diabetic nephropathy. In the present study, our aim was to investigate the effects of blood glucose fluctuation on the glomerular mesangal cells and its related mechanism. MATERIAL AND METHODS: Mesangial cells were divided into four groups: the normal glucose group (NG) cells were incubated in normal glucose conditions (5.6 mmol/l); the high glucose group (HG) cells were treated with 25 mmol/l; the glucose fluctuation (FG) group received 5.6 mmol/l and 25 mmol/l glucose repeated 3 times; the mannitol group (MG) received 5.6 mmol/l glucose plus 24.4 mmol/l mannitol as a control. Cell viability and apoptosis were detected, reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels were measured. Phosphorylated ser/thr protein kinase (P-AKT, phosphor-Ser473), phosphorylated glycogen synthase kinase-3β (P-GSK-3β, phosphor-Ser9) and cleaved cysteinyl aspartate-specific proteinase-3 (cleaved caspase-3) levels were assessed using western blot. RESULTS: Data suggested that mesangial cells in the FG group show higher cell viability in 12 h, and lower cell viability from 48 h. The FG group showed cell apoptosis accompanied by a significant MDA level increase and SOD activity decrease in 48 h. More importantly, glucose fluctuation could aggravate oxidative stress in glomerular mesangial cells. Furthermore, the P-AKT level was lower, and increased P-GSK-3β and cleaved caspase-3 levels were higher in the FG group than in the HG group. CONCLUSIONS: Glucose fluctuation aggravates mesangial cell apoptosis, which may be partly induced by activating oxidative stress and inhibiting the AKT signaling pathway. Termedia Publishing House 2019-04-30 2019-05 /pmc/articles/PMC6524177/ /pubmed/31110541 http://dx.doi.org/10.5114/aoms.2019.84739 Text en Copyright: © 2019 Termedia & Banach http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
spellingShingle Basic Research
Ying, Changjiang
Wang, Shanshan
Lu, Yan
Chen, Lei
Mao, Yizhen
Ling, Hongwei
Cheng, Xingbo
Zhou, Xiaoyan
Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway
title Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway
title_full Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway
title_fullStr Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway
title_full_unstemmed Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway
title_short Glucose fluctuation increased mesangial cell apoptosis related to AKT signal pathway
title_sort glucose fluctuation increased mesangial cell apoptosis related to akt signal pathway
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524177/
https://www.ncbi.nlm.nih.gov/pubmed/31110541
http://dx.doi.org/10.5114/aoms.2019.84739
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