Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome
Abstract Introduction Imeglimin, a glucose‐lowering agent targeting mitochondrial bioenergetics, decreases reactive oxygen species (ROS) overproduction and improves glucose homeostasis. We investigated whether this is associated with protective effects on metabolic syndrome‐related left ventricular...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-07-01
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| Series: | Endocrinology, Diabetes & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/edm2.128 |
| _version_ | 1818198670060814336 |
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| author | Marianne Lachaux Matthieu Soulié Mouad Hamzaoui Anaëlle Bailly Lionel Nicol Isabelle Rémy‐Jouet Sylvanie Renet Cathy Vendeville Pascale Gluais‐Dagorn Sophie Hallakou‐Bozec Christelle Monteil Vincent Richard Paul Mulder |
| author_facet | Marianne Lachaux Matthieu Soulié Mouad Hamzaoui Anaëlle Bailly Lionel Nicol Isabelle Rémy‐Jouet Sylvanie Renet Cathy Vendeville Pascale Gluais‐Dagorn Sophie Hallakou‐Bozec Christelle Monteil Vincent Richard Paul Mulder |
| author_sort | Marianne Lachaux |
| collection | DOAJ |
| description | Abstract Introduction Imeglimin, a glucose‐lowering agent targeting mitochondrial bioenergetics, decreases reactive oxygen species (ROS) overproduction and improves glucose homeostasis. We investigated whether this is associated with protective effects on metabolic syndrome‐related left ventricular (LV) and vascular dysfunctions. Methods We used Zucker fa/fa rats to assess the effects on LV function, LV tissue perfusion, LV oxidative stress and vascular function induced by imeglimin administered orally for 9 or 90 days at a dose of 150 mg/kg twice daily. Results Compared to untreated animals, 9‐ and 90‐day imeglimin treatment decreased LV end‐diastolic pressure and LV end‐diastolic pressure‐volume relation, increased LV tissue perfusion and decreased LV ROS production. Simultaneously, imeglimin restored acetylcholine‐mediated coronary relaxation and mesenteric flow‐mediated dilation. One hour after imeglimin administration, when glucose plasma levels were not yet modified, imeglimin reduced LV mitochondrial ROS production and improved LV function. Ninety‐day imeglimin treatment reduced related LV and kidney fibrosis and improved kidney function. Conclusion In a rat model, mimicking Human metabolic syndrome, imeglimin immediately countered metabolic syndrome‐related cardiac diastolic and vascular dysfunction by reducing oxidative stress/increased NO bioavailability and improving myocardial perfusion and after 90‐day treatment myocardial and kidney structure, effects that are, at least in part, independent from glucose control. |
| first_indexed | 2024-12-12T02:09:33Z |
| format | Article |
| id | doaj.art-64bc7ebebb374bd382dbaf000e2e59fd |
| institution | Directory Open Access Journal |
| issn | 2398-9238 |
| language | English |
| last_indexed | 2024-12-12T02:09:33Z |
| publishDate | 2020-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism |
| spelling | doaj.art-64bc7ebebb374bd382dbaf000e2e59fd2022-12-22T00:41:56ZengWileyEndocrinology, Diabetes & Metabolism2398-92382020-07-0133n/an/a10.1002/edm2.128Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndromeMarianne Lachaux0Matthieu Soulié1Mouad Hamzaoui2Anaëlle Bailly3Lionel Nicol4Isabelle Rémy‐Jouet5Sylvanie Renet6Cathy Vendeville7Pascale Gluais‐Dagorn8Sophie Hallakou‐Bozec9Christelle Monteil10Vincent Richard11Paul Mulder12UNIROUEN Inserm U1096 FHU‐REMOD‐VHF Normandie Univ Rouen FranceUNIROUEN UNICAEN ABTE Normandie Univ Rouen FranceUNIROUEN UNICAEN ABTE Normandie Univ Rouen FranceUNIROUEN Inserm U1096 FHU‐REMOD‐VHF Normandie Univ Rouen FranceUNIROUEN Inserm U1096 FHU‐REMOD‐VHF Normandie Univ Rouen FranceUNIROUEN Inserm U1096 FHU‐REMOD‐VHF Normandie Univ Rouen FranceUNIROUEN Inserm U1096 FHU‐REMOD‐VHF Normandie Univ Rouen FranceUNIROUEN UNICAEN ABTE Normandie Univ Rouen FrancePoxel S.A. Lyon FrancePoxel S.A. Lyon FranceUNIROUEN UNICAEN ABTE Normandie Univ Rouen FranceUNIROUEN Inserm U1096 FHU‐REMOD‐VHF Normandie Univ Rouen FranceUNIROUEN Inserm U1096 FHU‐REMOD‐VHF Normandie Univ Rouen FranceAbstract Introduction Imeglimin, a glucose‐lowering agent targeting mitochondrial bioenergetics, decreases reactive oxygen species (ROS) overproduction and improves glucose homeostasis. We investigated whether this is associated with protective effects on metabolic syndrome‐related left ventricular (LV) and vascular dysfunctions. Methods We used Zucker fa/fa rats to assess the effects on LV function, LV tissue perfusion, LV oxidative stress and vascular function induced by imeglimin administered orally for 9 or 90 days at a dose of 150 mg/kg twice daily. Results Compared to untreated animals, 9‐ and 90‐day imeglimin treatment decreased LV end‐diastolic pressure and LV end‐diastolic pressure‐volume relation, increased LV tissue perfusion and decreased LV ROS production. Simultaneously, imeglimin restored acetylcholine‐mediated coronary relaxation and mesenteric flow‐mediated dilation. One hour after imeglimin administration, when glucose plasma levels were not yet modified, imeglimin reduced LV mitochondrial ROS production and improved LV function. Ninety‐day imeglimin treatment reduced related LV and kidney fibrosis and improved kidney function. Conclusion In a rat model, mimicking Human metabolic syndrome, imeglimin immediately countered metabolic syndrome‐related cardiac diastolic and vascular dysfunction by reducing oxidative stress/increased NO bioavailability and improving myocardial perfusion and after 90‐day treatment myocardial and kidney structure, effects that are, at least in part, independent from glucose control.https://doi.org/10.1002/edm2.128cardiomyopathyimegliminrattype‐2 diabetes |
| spellingShingle | Marianne Lachaux Matthieu Soulié Mouad Hamzaoui Anaëlle Bailly Lionel Nicol Isabelle Rémy‐Jouet Sylvanie Renet Cathy Vendeville Pascale Gluais‐Dagorn Sophie Hallakou‐Bozec Christelle Monteil Vincent Richard Paul Mulder Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome Endocrinology, Diabetes & Metabolism cardiomyopathy imeglimin rat type‐2 diabetes |
| title | Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome |
| title_full | Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome |
| title_fullStr | Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome |
| title_full_unstemmed | Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome |
| title_short | Short‐and long‐term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome |
| title_sort | short and long term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome |
| topic | cardiomyopathy imeglimin rat type‐2 diabetes |
| url | https://doi.org/10.1002/edm2.128 |
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