Cargando…
PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells
Type 2 diabetes mellitus is characterized by insulin resistance and hypersecretion of insulin from the pancreas to compensate for decreased insulin sensitivity in the peripheral tissues. In later stages of the disease insulin-secreting beta cell degeneration commences and patients require insulin re...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Scientific and Technological Research Council of Turkey
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129068/ https://www.ncbi.nlm.nih.gov/pubmed/32256145 http://dx.doi.org/10.3906/biy-1909-20 |
_version_ | 1783516704604684288 |
---|---|
author | YALÇIN, Abdullah ŞARKICI, Gülçin KOLAÇ, Umut Kerem |
author_facet | YALÇIN, Abdullah ŞARKICI, Gülçin KOLAÇ, Umut Kerem |
author_sort | YALÇIN, Abdullah |
collection | PubMed |
description | Type 2 diabetes mellitus is characterized by insulin resistance and hypersecretion of insulin from the pancreas to compensate for decreased insulin sensitivity in the peripheral tissues. In later stages of the disease insulin-secreting beta cell degeneration commences and patients require insulin replacement therapy in order to accomplish proper regulation of their blood glucose. Endoplasmic reticulum (ER) stress in the beta cells is one of the factors contributing to this detrimental effect. Protein kinase R (PKR) is a cellular stress kinase activated by ER stress and contributing to degeneration of pancreatic islets. In order to determine whether inhibition of PKR activation by specific small molecule inhibitors of PKR ameliorates pancreatic insulin secretion capacity, we treated beta cells with two imidazole/oxindole-derived inhibitors of PKR kinase, imoxin (C16) and 2-aminopurine (2-AP), in the presence of ER stress. Our results demonstrate that PKR inhibition suppresses tunicamycin-mediated ER stress without altering the insulin production capacity of the cells. Palmitic acid-mediated suppression of insulin secretion, however, was subdued significantly by PKR inhibitor treatment through an ER stress-related mechanism. We suggest that PKR inhibitor treatment may be used to increase the insulin secretion capacity of the pancreas in later stages of diabetes. |
format | Online Article Text |
id | pubmed-7129068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Scientific and Technological Research Council of Turkey |
record_format | MEDLINE/PubMed |
spelling | pubmed-71290682020-04-06 PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells YALÇIN, Abdullah ŞARKICI, Gülçin KOLAÇ, Umut Kerem Turk J Biol Article Type 2 diabetes mellitus is characterized by insulin resistance and hypersecretion of insulin from the pancreas to compensate for decreased insulin sensitivity in the peripheral tissues. In later stages of the disease insulin-secreting beta cell degeneration commences and patients require insulin replacement therapy in order to accomplish proper regulation of their blood glucose. Endoplasmic reticulum (ER) stress in the beta cells is one of the factors contributing to this detrimental effect. Protein kinase R (PKR) is a cellular stress kinase activated by ER stress and contributing to degeneration of pancreatic islets. In order to determine whether inhibition of PKR activation by specific small molecule inhibitors of PKR ameliorates pancreatic insulin secretion capacity, we treated beta cells with two imidazole/oxindole-derived inhibitors of PKR kinase, imoxin (C16) and 2-aminopurine (2-AP), in the presence of ER stress. Our results demonstrate that PKR inhibition suppresses tunicamycin-mediated ER stress without altering the insulin production capacity of the cells. Palmitic acid-mediated suppression of insulin secretion, however, was subdued significantly by PKR inhibitor treatment through an ER stress-related mechanism. We suggest that PKR inhibitor treatment may be used to increase the insulin secretion capacity of the pancreas in later stages of diabetes. The Scientific and Technological Research Council of Turkey 2020-04-02 /pmc/articles/PMC7129068/ /pubmed/32256145 http://dx.doi.org/10.3906/biy-1909-20 Text en Copyright © 2020 The Author(s) This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Article YALÇIN, Abdullah ŞARKICI, Gülçin KOLAÇ, Umut Kerem PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells |
title | PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells |
title_full | PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells |
title_fullStr | PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells |
title_full_unstemmed | PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells |
title_short | PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells |
title_sort | pkr inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7129068/ https://www.ncbi.nlm.nih.gov/pubmed/32256145 http://dx.doi.org/10.3906/biy-1909-20 |
work_keys_str_mv | AT yalcinabdullah pkrinhibitorssuppressendoplasmicreticulumstressandsubdueglucolipotoxicitymediatedimpairmentofinsulinsecretioninpancreaticbetacells AT sarkicigulcin pkrinhibitorssuppressendoplasmicreticulumstressandsubdueglucolipotoxicitymediatedimpairmentofinsulinsecretioninpancreaticbetacells AT kolacumutkerem pkrinhibitorssuppressendoplasmicreticulumstressandsubdueglucolipotoxicitymediatedimpairmentofinsulinsecretioninpancreaticbetacells |