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Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications
The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. Here, we thus combined high-fat/high-fructose diet, with multiple low-dose injections of streptozotocin (HF/HF/Stz) to emulate the long-term complications of T2DM. HF/HF/Stz rats, monitored over 56 weeks, exhibi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765114/ https://www.ncbi.nlm.nih.gov/pubmed/29323186 http://dx.doi.org/10.1038/s41598-017-18896-5 |
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author | Barrière, David André Noll, Christophe Roussy, Geneviève Lizotte, Farah Kessai, Anissa Kirby, Karyn Belleville, Karine Beaudet, Nicolas Longpré, Jean-Michel Carpentier, André C. Geraldes, Pedro Sarret, Philippe |
author_facet | Barrière, David André Noll, Christophe Roussy, Geneviève Lizotte, Farah Kessai, Anissa Kirby, Karyn Belleville, Karine Beaudet, Nicolas Longpré, Jean-Michel Carpentier, André C. Geraldes, Pedro Sarret, Philippe |
author_sort | Barrière, David André |
collection | PubMed |
description | The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. Here, we thus combined high-fat/high-fructose diet, with multiple low-dose injections of streptozotocin (HF/HF/Stz) to emulate the long-term complications of T2DM. HF/HF/Stz rats, monitored over 56 weeks, exhibited metabolic dysfunctions associated with the different stages of the T2DM disease progression in humans: an early prediabetic phase characterized by an hyperinsulinemic period with modest dysglycemia, followed by a late stage of T2DM with frank hyperglycemia, normalization of insulinemia, marked dyslipidemia, hepatic fibrosis and pancreatic β-cell failure. Histopathological analyses combined to [(18)F]-FDG PET imaging further demonstrated the presence of several end-organ long-term complications, including reduction in myocardial glucose utilization, renal dysfunction as well as microvascular neuropathy and retinopathy. We also provide for the first time a comprehensive µ-PET whole brain imaging of the changes in glucose metabolic activity within discrete cerebral regions in HF/HF/Stz diabetic rats. Altogether, we developed and characterized a unique non-genetic preclinical model of T2DM adapted to the current diet and lifestyle that recapitulates the major metabolic features of the disease progression, from insulin resistance to pancreatic β-cell dysfunction, and closely mimicking the target-organ damage occurring in type 2 diabetic patients at advanced stages. |
format | Online Article Text |
id | pubmed-5765114 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57651142018-01-17 Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications Barrière, David André Noll, Christophe Roussy, Geneviève Lizotte, Farah Kessai, Anissa Kirby, Karyn Belleville, Karine Beaudet, Nicolas Longpré, Jean-Michel Carpentier, André C. Geraldes, Pedro Sarret, Philippe Sci Rep Article The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. Here, we thus combined high-fat/high-fructose diet, with multiple low-dose injections of streptozotocin (HF/HF/Stz) to emulate the long-term complications of T2DM. HF/HF/Stz rats, monitored over 56 weeks, exhibited metabolic dysfunctions associated with the different stages of the T2DM disease progression in humans: an early prediabetic phase characterized by an hyperinsulinemic period with modest dysglycemia, followed by a late stage of T2DM with frank hyperglycemia, normalization of insulinemia, marked dyslipidemia, hepatic fibrosis and pancreatic β-cell failure. Histopathological analyses combined to [(18)F]-FDG PET imaging further demonstrated the presence of several end-organ long-term complications, including reduction in myocardial glucose utilization, renal dysfunction as well as microvascular neuropathy and retinopathy. We also provide for the first time a comprehensive µ-PET whole brain imaging of the changes in glucose metabolic activity within discrete cerebral regions in HF/HF/Stz diabetic rats. Altogether, we developed and characterized a unique non-genetic preclinical model of T2DM adapted to the current diet and lifestyle that recapitulates the major metabolic features of the disease progression, from insulin resistance to pancreatic β-cell dysfunction, and closely mimicking the target-organ damage occurring in type 2 diabetic patients at advanced stages. Nature Publishing Group UK 2018-01-11 /pmc/articles/PMC5765114/ /pubmed/29323186 http://dx.doi.org/10.1038/s41598-017-18896-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Barrière, David André Noll, Christophe Roussy, Geneviève Lizotte, Farah Kessai, Anissa Kirby, Karyn Belleville, Karine Beaudet, Nicolas Longpré, Jean-Michel Carpentier, André C. Geraldes, Pedro Sarret, Philippe Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications |
title | Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications |
title_full | Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications |
title_fullStr | Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications |
title_full_unstemmed | Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications |
title_short | Combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications |
title_sort | combination of high-fat/high-fructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765114/ https://www.ncbi.nlm.nih.gov/pubmed/29323186 http://dx.doi.org/10.1038/s41598-017-18896-5 |
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