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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/12/1270 |
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| author | Amal Essaouiba Rachid Jellali Françoise Gilard Bertrand Gakière Teru Okitsu Cécile Legallais Yasuyuki Sakai Eric Leclerc |
| author_facet | Amal Essaouiba Rachid Jellali Françoise Gilard Bertrand Gakière Teru Okitsu Cécile Legallais Yasuyuki Sakai Eric Leclerc |
| author_sort | Amal Essaouiba |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T16:06:16Z |
| format | Article |
| id | doaj.art-83958ebdd1a2410b8ed495eb0053d346 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T16:06:16Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-83958ebdd1a2410b8ed495eb0053d3462023-11-24T16:38:37ZengMDPI AGMetabolites2218-19892022-12-011212127010.3390/metabo12121270Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic BiochipAmal Essaouiba0Rachid Jellali1Françoise Gilard2Bertrand Gakière3Teru Okitsu4Cécile Legallais5Yasuyuki Sakai6Eric Leclerc7Biomechanics and Bioengineering, CNRS, Université de Technologie de Compiègne, Centre de Recherche Royallieu CS 60319, 60203 Compiègne, FranceBiomechanics and Bioengineering, CNRS, Université de Technologie de Compiègne, Centre de Recherche Royallieu CS 60319, 60203 Compiègne, FrancePlateforme Métabolisme-Métabolome, Institute of Plant Sciences Paris-Saclay (IPS2), Université Paris-Saclay, CNRS, INRAE, Université Evry, Université Paris Cité, Bâtiment 360, Avenue des Sciences, 91190 Gif sur Yvette, FrancePlateforme Métabolisme-Métabolome, Institute of Plant Sciences Paris-Saclay (IPS2), Université Paris-Saclay, CNRS, INRAE, Université Evry, Université Paris Cité, Bâtiment 360, Avenue des Sciences, 91190 Gif sur Yvette, FranceInstitute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, JapanBiomechanics and Bioengineering, CNRS, Université de Technologie de Compiègne, Centre de Recherche Royallieu CS 60319, 60203 Compiègne, FranceCNRS IRL 2820, Laboratory for Integrated Micro Mechatronic Systems, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, JapanBiomechanics and Bioengineering, CNRS, Université de Technologie de Compiègne, Centre de Recherche Royallieu CS 60319, 60203 Compiègne, FranceDiabetes 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.https://www.mdpi.com/2218-1989/12/12/1270microfluidic culturebiochipislets of Langerhansexometabolomediabetes |
| spellingShingle | Amal Essaouiba Rachid Jellali Françoise Gilard Bertrand Gakière Teru Okitsu Cécile Legallais Yasuyuki Sakai Eric Leclerc Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip Metabolites microfluidic culture biochip islets of Langerhans exometabolome diabetes |
| 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 | microfluidic culture biochip islets of Langerhans exometabolome diabetes |
| url | https://www.mdpi.com/2218-1989/12/12/1270 |
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