Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice
Abstract Background Albumin is the most abundant protein in serum and serves as a transporter of free fatty acids (FFA) in blood vessels. In type 2 diabetes mellitus (T2DM) patients, the reduced serum albumin level is a risk factor for T2DM development and progression, although this conclusion is co...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-03957-3 |
| _version_ | 1811165783446781952 |
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| author | Hongyi Liu Anji Ju Xuan Dong Zongrui Luo Jiaze Tang Boyuan Ma Yan Fu Yongzhang Luo |
| author_facet | Hongyi Liu Anji Ju Xuan Dong Zongrui Luo Jiaze Tang Boyuan Ma Yan Fu Yongzhang Luo |
| author_sort | Hongyi Liu |
| collection | DOAJ |
| description | Abstract Background Albumin is the most abundant protein in serum and serves as a transporter of free fatty acids (FFA) in blood vessels. In type 2 diabetes mellitus (T2DM) patients, the reduced serum albumin level is a risk factor for T2DM development and progression, although this conclusion is controversial. Moreover, there is no study on the effects and mechanisms of albumin administration to relieve T2DM. We examined whether the administration of young and undamaged recombinant albumin can alleviate T2DM in mice. Methods The serum albumin levels and metabolic phenotypes including fasting blood glucose, glucose tolerance tests, and glucose-stimulated insulin secretion were studied in db/db mice or diet-induced obesity mice treated with saline or young, undamaged, and ultrapure rMSA. Apoptosis assays were performed at tissue and cell levels to determine the function of rMSA on islet β cell protection. Metabolic flux and glucose uptake assays were employed to investigate metabolic changes in saline-treated or rMSA-treated mouse hepatocytes and compared their sensitivity to insulin treatments. Results In this study, treatment of T2DM mice with young, undamaged, and ultrapure recombinant mouse serum albumin (rMSA) increased their serum albumin levels, which resulted in a reversal of the disease including reduced fasting blood glucose levels, improved glucose tolerance, increased glucose-stimulated insulin secretion, and alleviated islet atrophy. At the cellular level, rMSA improved glucose uptake and glycolysis in hepatocytes. Mechanistically, rMSA reduced the binding between CAV1 and EGFR to increase EGFR activation leading to PI3K-AKT activation. Furthermore, rMSA extracellularly reduced the rate of fatty acid uptake by islet β-cells, which relieved the accumulation of intracellular ceramide, endoplasmic reticulum stress, and apoptosis. This study provided the first clear demonstration that injections of rMSA can alleviate T2DM in mice. Conclusion Our study demonstrates that increasing serum albumin levels can promote glucose homeostasis and protect islet β cells, which alleviates T2DM. |
| first_indexed | 2024-04-10T15:42:12Z |
| format | Article |
| id | doaj.art-90dd78636b5f455fb39bcc750e31986e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-10T15:42:12Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-90dd78636b5f455fb39bcc750e31986e2023-02-12T12:21:03ZengBMCJournal of Translational Medicine1479-58762023-02-0121111810.1186/s12967-023-03957-3Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in miceHongyi Liu0Anji Ju1Xuan Dong2Zongrui Luo3Jiaze Tang4Boyuan Ma5Yan Fu6Yongzhang Luo7School of Life Sciences, Tsinghua UniversitySchool of Life Sciences, Tsinghua UniversitySchool of Life Sciences, Tsinghua UniversitySchool of Life Sciences, Tsinghua UniversitySchool of Life Sciences, Tsinghua UniversitySchool of Life Sciences, Tsinghua UniversitySchool of Life Sciences, Tsinghua UniversitySchool of Life Sciences, Tsinghua UniversityAbstract Background Albumin is the most abundant protein in serum and serves as a transporter of free fatty acids (FFA) in blood vessels. In type 2 diabetes mellitus (T2DM) patients, the reduced serum albumin level is a risk factor for T2DM development and progression, although this conclusion is controversial. Moreover, there is no study on the effects and mechanisms of albumin administration to relieve T2DM. We examined whether the administration of young and undamaged recombinant albumin can alleviate T2DM in mice. Methods The serum albumin levels and metabolic phenotypes including fasting blood glucose, glucose tolerance tests, and glucose-stimulated insulin secretion were studied in db/db mice or diet-induced obesity mice treated with saline or young, undamaged, and ultrapure rMSA. Apoptosis assays were performed at tissue and cell levels to determine the function of rMSA on islet β cell protection. Metabolic flux and glucose uptake assays were employed to investigate metabolic changes in saline-treated or rMSA-treated mouse hepatocytes and compared their sensitivity to insulin treatments. Results In this study, treatment of T2DM mice with young, undamaged, and ultrapure recombinant mouse serum albumin (rMSA) increased their serum albumin levels, which resulted in a reversal of the disease including reduced fasting blood glucose levels, improved glucose tolerance, increased glucose-stimulated insulin secretion, and alleviated islet atrophy. At the cellular level, rMSA improved glucose uptake and glycolysis in hepatocytes. Mechanistically, rMSA reduced the binding between CAV1 and EGFR to increase EGFR activation leading to PI3K-AKT activation. Furthermore, rMSA extracellularly reduced the rate of fatty acid uptake by islet β-cells, which relieved the accumulation of intracellular ceramide, endoplasmic reticulum stress, and apoptosis. This study provided the first clear demonstration that injections of rMSA can alleviate T2DM in mice. Conclusion Our study demonstrates that increasing serum albumin levels can promote glucose homeostasis and protect islet β cells, which alleviates T2DM.https://doi.org/10.1186/s12967-023-03957-3rMSAType 2 diabetes mellitusGlycolysisβ-Cell apoptosisLipotoxicity |
| spellingShingle | Hongyi Liu Anji Ju Xuan Dong Zongrui Luo Jiaze Tang Boyuan Ma Yan Fu Yongzhang Luo Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice Journal of Translational Medicine rMSA Type 2 diabetes mellitus Glycolysis β-Cell apoptosis Lipotoxicity |
| title | Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice |
| title_full | Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice |
| title_fullStr | Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice |
| title_full_unstemmed | Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice |
| title_short | Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice |
| title_sort | young and undamaged recombinant albumin alleviates t2dm by improving hepatic glycolysis through egfr and protecting islet β cells in mice |
| topic | rMSA Type 2 diabetes mellitus Glycolysis β-Cell apoptosis Lipotoxicity |
| url | https://doi.org/10.1186/s12967-023-03957-3 |
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