Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans
Biliverdin reductase-A (BVRA) is involved in the regulation of insulin signaling and the maintenance of glucose homeostasis. Previous research showed that BVRA alterations are associated with the aberrant activation of insulin signaling in dysmetabolic conditions. However, whether BVRA protein level...
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| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7282 |
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| author | Flavia Agata Cimini Antonella Tramutola Ilaria Barchetta Valentina Ceccarelli Elena Gangitano Simona Lanzillotta Chiara Lanzillotta Maria Gisella Cavallo Eugenio Barone |
| author_facet | Flavia Agata Cimini Antonella Tramutola Ilaria Barchetta Valentina Ceccarelli Elena Gangitano Simona Lanzillotta Chiara Lanzillotta Maria Gisella Cavallo Eugenio Barone |
| author_sort | Flavia Agata Cimini |
| collection | DOAJ |
| description | Biliverdin reductase-A (BVRA) is involved in the regulation of insulin signaling and the maintenance of glucose homeostasis. Previous research showed that BVRA alterations are associated with the aberrant activation of insulin signaling in dysmetabolic conditions. However, whether BVRA protein levels change dynamically within the cells in response to insulin and/or glucose remains an open question. To this aim, we evaluated changes of intracellular BVRA levels in peripheral blood mononuclear cells (PBMC) collected during the oral glucose tolerance test (OGTT) in a group of subjects with different levels of insulin sensitivity. Furthermore, we looked for significant correlations with clinical measures. Our data show that BVRA levels change dynamically during the OGTT in response to insulin, and greater BVRA variations occur in those subjects with lower insulin sensitivity. Changes of BVRA significantly correlate with indexes of increased insulin resistance and insulin secretion (HOMA-IR, HOMA-β, and insulinogenic index). At the multivariate regression analysis, the insulinogenic index independently predicted increased BVRA area under curve (AUC) during the OGTT. This pilot study showed, for the first time, that intracellular BVRA protein levels change in response to insulin during OGTT and are greater in subjects with lower insulin sensitivity, supporting the role of BVR-A in the dynamic regulation of the insulin signaling pathway. |
| first_indexed | 2024-03-11T04:56:06Z |
| format | Article |
| id | doaj.art-69b6df6be6124c2fa78e7fd8d025848f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:56:06Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-69b6df6be6124c2fa78e7fd8d025848f2023-11-17T19:38:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248728210.3390/ijms24087282Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in HumansFlavia Agata Cimini0Antonella Tramutola1Ilaria Barchetta2Valentina Ceccarelli3Elena Gangitano4Simona Lanzillotta5Chiara Lanzillotta6Maria Gisella Cavallo7Eugenio Barone8Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, 00185 Rome, ItalyBiliverdin reductase-A (BVRA) is involved in the regulation of insulin signaling and the maintenance of glucose homeostasis. Previous research showed that BVRA alterations are associated with the aberrant activation of insulin signaling in dysmetabolic conditions. However, whether BVRA protein levels change dynamically within the cells in response to insulin and/or glucose remains an open question. To this aim, we evaluated changes of intracellular BVRA levels in peripheral blood mononuclear cells (PBMC) collected during the oral glucose tolerance test (OGTT) in a group of subjects with different levels of insulin sensitivity. Furthermore, we looked for significant correlations with clinical measures. Our data show that BVRA levels change dynamically during the OGTT in response to insulin, and greater BVRA variations occur in those subjects with lower insulin sensitivity. Changes of BVRA significantly correlate with indexes of increased insulin resistance and insulin secretion (HOMA-IR, HOMA-β, and insulinogenic index). At the multivariate regression analysis, the insulinogenic index independently predicted increased BVRA area under curve (AUC) during the OGTT. This pilot study showed, for the first time, that intracellular BVRA protein levels change in response to insulin during OGTT and are greater in subjects with lower insulin sensitivity, supporting the role of BVR-A in the dynamic regulation of the insulin signaling pathway.https://www.mdpi.com/1422-0067/24/8/7282biliverdin reductase-Ainsulin signalingmetabolismobesitydiabetes |
| spellingShingle | Flavia Agata Cimini Antonella Tramutola Ilaria Barchetta Valentina Ceccarelli Elena Gangitano Simona Lanzillotta Chiara Lanzillotta Maria Gisella Cavallo Eugenio Barone Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans International Journal of Molecular Sciences biliverdin reductase-A insulin signaling metabolism obesity diabetes |
| title | Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans |
| title_full | Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans |
| title_fullStr | Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans |
| title_full_unstemmed | Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans |
| title_short | Dynamic Changes of BVRA Protein Levels Occur in Response to Insulin: A Pilot Study in Humans |
| title_sort | dynamic changes of bvra protein levels occur in response to insulin a pilot study in humans |
| topic | biliverdin reductase-A insulin signaling metabolism obesity diabetes |
| url | https://www.mdpi.com/1422-0067/24/8/7282 |
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