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Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip

Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic tissue response to patholo...

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Autores principales: Essaouiba, Amal, Jellali, Rachid, Gilard, Françoise, Gakière, Bertrand, Okitsu, Teru, Legallais, Cécile, Sakai, Yasuyuki, Leclerc, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786643/
https://www.ncbi.nlm.nih.gov/pubmed/36557308
http://dx.doi.org/10.3390/metabo12121270
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author Essaouiba, Amal
Jellali, Rachid
Gilard, Françoise
Gakière, Bertrand
Okitsu, Teru
Legallais, Cécile
Sakai, Yasuyuki
Leclerc, Eric
author_facet Essaouiba, Amal
Jellali, Rachid
Gilard, Françoise
Gakière, Bertrand
Okitsu, Teru
Legallais, Cécile
Sakai, Yasuyuki
Leclerc, Eric
author_sort Essaouiba, Amal
collection PubMed
description Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic tissue response to pathological situations and identify therapeutic solutions. Of all the in vitro promising models, cell culture in microfluidic biochip allows the reproduction of in-vivo-like micro-environments. Here, we cultured rat islets of Langerhans using dynamic cultures in microfluidic biochips. The dynamic cultures were compared to static islets cultures in Petri. The islets’ exometabolomic signatures, with and without GLP1 and isradipine treatments, were characterized by GC-MS. Compared to Petri, biochip culture contributes to maintaining high secretions of insulin, C-peptide and glucagon. The exometabolomic profiling revealed 22 and 18 metabolites differentially expressed between Petri and biochip on Day 3 and 5. These metabolites illustrated the increase in lipid metabolism, the perturbation of the pentose phosphate pathway and the TCA cycle in biochip. After drug stimulations, the exometabolome of biochip culture appeared more perturbed than the Petri exometabolome. The GLP1 contributed to the increase in the levels of glycolysis, pentose phosphate and glutathione pathways intermediates, whereas isradipine led to reduced levels of lipids and carbohydrates.
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spelling pubmed-97866432022-12-24 Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip Essaouiba, Amal Jellali, Rachid Gilard, Françoise Gakière, Bertrand Okitsu, Teru Legallais, Cécile Sakai, Yasuyuki Leclerc, Eric Metabolites Article Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic tissue response to pathological situations and identify therapeutic solutions. Of all the in vitro promising models, cell culture in microfluidic biochip allows the reproduction of in-vivo-like micro-environments. Here, we cultured rat islets of Langerhans using dynamic cultures in microfluidic biochips. The dynamic cultures were compared to static islets cultures in Petri. The islets’ exometabolomic signatures, with and without GLP1 and isradipine treatments, were characterized by GC-MS. Compared to Petri, biochip culture contributes to maintaining high secretions of insulin, C-peptide and glucagon. The exometabolomic profiling revealed 22 and 18 metabolites differentially expressed between Petri and biochip on Day 3 and 5. These metabolites illustrated the increase in lipid metabolism, the perturbation of the pentose phosphate pathway and the TCA cycle in biochip. After drug stimulations, the exometabolome of biochip culture appeared more perturbed than the Petri exometabolome. The GLP1 contributed to the increase in the levels of glycolysis, pentose phosphate and glutathione pathways intermediates, whereas isradipine led to reduced levels of lipids and carbohydrates. MDPI 2022-12-15 /pmc/articles/PMC9786643/ /pubmed/36557308 http://dx.doi.org/10.3390/metabo12121270 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Essaouiba, Amal
Jellali, Rachid
Gilard, Françoise
Gakière, Bertrand
Okitsu, Teru
Legallais, Cécile
Sakai, Yasuyuki
Leclerc, Eric
Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
title Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
title_full Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
title_fullStr Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
title_full_unstemmed Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
title_short Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
title_sort investigation of the exometabolomic profiles of rat islets of langerhans cultured in microfluidic biochip
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9786643/
https://www.ncbi.nlm.nih.gov/pubmed/36557308
http://dx.doi.org/10.3390/metabo12121270
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