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Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass
Although convincing in genetic models, the relevance of β-cell insulin resistance in diet-induced type 2 diabetes (T2DM) remains unclear. Exemplified by diabetes-prone, male, C57B1/6J mice being fed different combinations of Western-style diet, we show that β-cell insulin resistance occurs early dur...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355083/ https://www.ncbi.nlm.nih.gov/pubmed/29957055 http://dx.doi.org/10.1096/fj.201800826R |
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author | Paschen, Meike Moede, Tilo Valladolid-Acebes, Ismael Leibiger, Barbara Moruzzi, Noah Jacob, Stefan García-Prieto, Concha F. Brismar, Kerstin Leibiger, Ingo B. Berggren, Per-Olof |
author_facet | Paschen, Meike Moede, Tilo Valladolid-Acebes, Ismael Leibiger, Barbara Moruzzi, Noah Jacob, Stefan García-Prieto, Concha F. Brismar, Kerstin Leibiger, Ingo B. Berggren, Per-Olof |
author_sort | Paschen, Meike |
collection | PubMed |
description | Although convincing in genetic models, the relevance of β-cell insulin resistance in diet-induced type 2 diabetes (T2DM) remains unclear. Exemplified by diabetes-prone, male, C57B1/6J mice being fed different combinations of Western-style diet, we show that β-cell insulin resistance occurs early during T2DM progression and is due to a combination of lipotoxicity and increased β-cell workload. Within 8 wk of being fed a high-fat, high-sucrose diet, mice became obese, developed impaired insulin and glucose tolerances, and displayed noncompensatory insulin release, due, at least in part, to reduced expression of syntaxin-1A. Through reporter islets transplanted to the anterior chamber of the eye, we demonstrated a concomitant loss of functional β-cell mass. When mice were changed from diabetogenic diet to normal chow diet, the diabetes phenotype was reversed, suggesting a remarkable plasticity of functional β-cell mass in the early phase of T2DM development. Our data reinforce the relevance of diet composition as an environmental factor determining different routes of diabetes progression in a given genetic background. Employing the in vivo reporter islet–monitoring approach will allow researchers to define key times in the dynamics of reversible loss of functional β-cell mass and, thus, to investigate the underlying, molecular mechanisms involved in the progression toward T2DM manifestation.—Paschen, M., Moede, T., Valladolid-Acebes, I., Leibiger, B., Moruzzi, N., Jacob, S., García-Prieto, C. F., Brismar, K., Leibiger, I. B., Berggren, P.-O. Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass. |
format | Online Article Text |
id | pubmed-6355083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-63550832019-02-05 Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass Paschen, Meike Moede, Tilo Valladolid-Acebes, Ismael Leibiger, Barbara Moruzzi, Noah Jacob, Stefan García-Prieto, Concha F. Brismar, Kerstin Leibiger, Ingo B. Berggren, Per-Olof FASEB J Research Although convincing in genetic models, the relevance of β-cell insulin resistance in diet-induced type 2 diabetes (T2DM) remains unclear. Exemplified by diabetes-prone, male, C57B1/6J mice being fed different combinations of Western-style diet, we show that β-cell insulin resistance occurs early during T2DM progression and is due to a combination of lipotoxicity and increased β-cell workload. Within 8 wk of being fed a high-fat, high-sucrose diet, mice became obese, developed impaired insulin and glucose tolerances, and displayed noncompensatory insulin release, due, at least in part, to reduced expression of syntaxin-1A. Through reporter islets transplanted to the anterior chamber of the eye, we demonstrated a concomitant loss of functional β-cell mass. When mice were changed from diabetogenic diet to normal chow diet, the diabetes phenotype was reversed, suggesting a remarkable plasticity of functional β-cell mass in the early phase of T2DM development. Our data reinforce the relevance of diet composition as an environmental factor determining different routes of diabetes progression in a given genetic background. Employing the in vivo reporter islet–monitoring approach will allow researchers to define key times in the dynamics of reversible loss of functional β-cell mass and, thus, to investigate the underlying, molecular mechanisms involved in the progression toward T2DM manifestation.—Paschen, M., Moede, T., Valladolid-Acebes, I., Leibiger, B., Moruzzi, N., Jacob, S., García-Prieto, C. F., Brismar, K., Leibiger, I. B., Berggren, P.-O. Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass. Federation of American Societies for Experimental Biology 2019-01 2018-06-29 /pmc/articles/PMC6355083/ /pubmed/29957055 http://dx.doi.org/10.1096/fj.201800826R Text en © The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paschen, Meike Moede, Tilo Valladolid-Acebes, Ismael Leibiger, Barbara Moruzzi, Noah Jacob, Stefan García-Prieto, Concha F. Brismar, Kerstin Leibiger, Ingo B. Berggren, Per-Olof Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass |
title | Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass |
title_full | Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass |
title_fullStr | Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass |
title_full_unstemmed | Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass |
title_short | Diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass |
title_sort | diet-induced β-cell insulin resistance results in reversible loss of functional β-cell mass |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355083/ https://www.ncbi.nlm.nih.gov/pubmed/29957055 http://dx.doi.org/10.1096/fj.201800826R |
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