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SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry
Type 1 diabetes (T1D) results in the loss of pancreatic beta cells and subsequent loss of insulin production. Exogenous insulin is the only effective treatment, but there is still no cure or interventional therapy available to inhibit progression of T1D. Successful T1D interventional therapy must pr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209592/ http://dx.doi.org/10.1210/jendso/bvaa046.1937 |
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author | Tawfik, Arielle Elizabeth Guergues, Jennifer Stevens, Stanley M Burkhardt, Brant Roger |
author_facet | Tawfik, Arielle Elizabeth Guergues, Jennifer Stevens, Stanley M Burkhardt, Brant Roger |
author_sort | Tawfik, Arielle Elizabeth |
collection | PubMed |
description | Type 1 diabetes (T1D) results in the loss of pancreatic beta cells and subsequent loss of insulin production. Exogenous insulin is the only effective treatment, but there is still no cure or interventional therapy available to inhibit progression of T1D. Successful T1D interventional therapy must protect pancreatic beta cells from autoimmunity while enhancing beta cell survival and function. Our data suggests Cornus officinalis (CO) may be a candidate for interventional therapy to protect pancreatic beta cells from autoimmune attack and increase their function. CO has been used in traditional Chinese medicine (TCM) for over 2,000 years and has shown characteristics of anti-diabetic effects in vitro and in vivo but never examined in the application of T1D. Our prior publication (Mol. and Cell. Endo.2019:494:110491), has shown increased proliferation and protection against Th1 cytokine attack upon CO treatment using a human pancreatic beta cell line, 1.1B4. From this, we sought to define precise molecular mechanism by employing a global and phosphorylation mass spectrometry (MS) approach. We applied CO to 1.1B4 cells for 2, 6, 12, and 24h then collected the cell lysates for MS analysis. Our global MS analysis revealed a 12-fold increase in beta cell functional regulator, IGFBP2, at multiple time points. IGFBP2 has been shown to display a T2D protective effect and regulate glucose metabolism. The ingenuity pathway analysis program (IPA) predicted an increase in insulin starting at 2h and the NRF2-mediated oxidative stress pathway at 12h and 24h. Furthermore, NRF2 is an upstream regulator of P62 which was significantly hyperphosphorylated at multiple timepoints from our MS analysis. Nrf2 is responsible for activating antioxidant enzymes upon oxidative stress, which is caused by proinflammatory cytokines in T1D. P62 aids in this pathway by targeting proteins for autophagy upon oxidative stress in order to keep cellular homeostasis within beta cells rather than cells progressing through apoptosis. Autophagy is critical for beta cell function and survival as it promotes survival under beta cell stress which would otherwise lead to cell death. The recovery and protection of autophagy in beta cells of patients in the pre-diagnosed stages of T1D could provide a beneficial interventional therapy in order to delay or inhibit the onset of T1D. Altogether, our proteomic analysis revealed an increase in IGFBP2 and predicted an increase in the NRf2-mediated oxidative stress pathway upon CO induction. Further analysis will examine the IGFBP2 and Nrf2-mediated oxidative pathway as a mechanism of CO induced protective and proliferative effects in pancreatic beta cells. |
format | Online Article Text |
id | pubmed-7209592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72095922020-05-13 SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry Tawfik, Arielle Elizabeth Guergues, Jennifer Stevens, Stanley M Burkhardt, Brant Roger J Endocr Soc Diabetes Mellitus and Glucose Metabolism Type 1 diabetes (T1D) results in the loss of pancreatic beta cells and subsequent loss of insulin production. Exogenous insulin is the only effective treatment, but there is still no cure or interventional therapy available to inhibit progression of T1D. Successful T1D interventional therapy must protect pancreatic beta cells from autoimmunity while enhancing beta cell survival and function. Our data suggests Cornus officinalis (CO) may be a candidate for interventional therapy to protect pancreatic beta cells from autoimmune attack and increase their function. CO has been used in traditional Chinese medicine (TCM) for over 2,000 years and has shown characteristics of anti-diabetic effects in vitro and in vivo but never examined in the application of T1D. Our prior publication (Mol. and Cell. Endo.2019:494:110491), has shown increased proliferation and protection against Th1 cytokine attack upon CO treatment using a human pancreatic beta cell line, 1.1B4. From this, we sought to define precise molecular mechanism by employing a global and phosphorylation mass spectrometry (MS) approach. We applied CO to 1.1B4 cells for 2, 6, 12, and 24h then collected the cell lysates for MS analysis. Our global MS analysis revealed a 12-fold increase in beta cell functional regulator, IGFBP2, at multiple time points. IGFBP2 has been shown to display a T2D protective effect and regulate glucose metabolism. The ingenuity pathway analysis program (IPA) predicted an increase in insulin starting at 2h and the NRF2-mediated oxidative stress pathway at 12h and 24h. Furthermore, NRF2 is an upstream regulator of P62 which was significantly hyperphosphorylated at multiple timepoints from our MS analysis. Nrf2 is responsible for activating antioxidant enzymes upon oxidative stress, which is caused by proinflammatory cytokines in T1D. P62 aids in this pathway by targeting proteins for autophagy upon oxidative stress in order to keep cellular homeostasis within beta cells rather than cells progressing through apoptosis. Autophagy is critical for beta cell function and survival as it promotes survival under beta cell stress which would otherwise lead to cell death. The recovery and protection of autophagy in beta cells of patients in the pre-diagnosed stages of T1D could provide a beneficial interventional therapy in order to delay or inhibit the onset of T1D. Altogether, our proteomic analysis revealed an increase in IGFBP2 and predicted an increase in the NRf2-mediated oxidative stress pathway upon CO induction. Further analysis will examine the IGFBP2 and Nrf2-mediated oxidative pathway as a mechanism of CO induced protective and proliferative effects in pancreatic beta cells. Oxford University Press 2020-05-08 /pmc/articles/PMC7209592/ http://dx.doi.org/10.1210/jendso/bvaa046.1937 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Diabetes Mellitus and Glucose Metabolism Tawfik, Arielle Elizabeth Guergues, Jennifer Stevens, Stanley M Burkhardt, Brant Roger SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry |
title | SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry |
title_full | SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry |
title_fullStr | SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry |
title_full_unstemmed | SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry |
title_short | SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry |
title_sort | sun-645 cornus officinalis promotes igfbp2 and autophagy in human 1.1b4 pancreatic cell line as revealed by employing a global proteomic approach via mass spectrometry |
topic | Diabetes Mellitus and Glucose Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209592/ http://dx.doi.org/10.1210/jendso/bvaa046.1937 |
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