Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration
Progressive loss and dysfunction of islet β-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rRe...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10584 |
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| author | Luting Yu Liang Li Junli Liu Hao Sun Xiang Li Hanyu Xiao Martin Omondi Alfred Min Wang Xuri Wu Yan Gao Chen Luo |
| author_facet | Luting Yu Liang Li Junli Liu Hao Sun Xiang Li Hanyu Xiao Martin Omondi Alfred Min Wang Xuri Wu Yan Gao Chen Luo |
| author_sort | Luting Yu |
| collection | DOAJ |
| description | Progressive loss and dysfunction of islet β-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rReg3α) and proved that it protects against acute pancreatitis in mice. Whether rReg3α protects islet β-cells in diabetes has been elusive. In the present study, rReg3α stimulated MIN6 cell proliferation and resisted STZ-caused cell death. The protective effect of rReg3α was also found in mouse primary islets. In BALB/c mice, rReg3α administration largely alleviated STZ-induced diabetes by the preservation of β-cell mass. The protective mechanism could be attributed to Akt/Bcl-2/-xL activation and GRP78 upregulation. Scattered insulin-expressing cells and clusters with small size, low insulin density, and exocrine distribution were observed and considered to be neogenic. In isolated acinar cells with wheat germ agglutinin (WGA) labeling, rReg3α treatment generated insulin-producing cells through Stat3/Ngn3 signaling, but these cells were not fully functional in response to glucose stimulation. Our results demonstrated that rReg3α resists STZ-induced β-cell death and promotes β-cell regeneration. rReg3α could serve as a potential drug for β-cell maintenance in anti-diabetic treatment. |
| first_indexed | 2024-03-09T23:46:16Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:46:16Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e9fa14d40ed54eef982bcd27cb9948b02023-11-23T16:44:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181058410.3390/ijms231810584Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell RegenerationLuting Yu0Liang Li1Junli Liu2Hao Sun3Xiang Li4Hanyu Xiao5Martin Omondi Alfred6Min Wang7Xuri Wu8Yan Gao9Chen Luo10School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaMeDiC Program, The Research Institute of McGill University Health Centre, Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, QC H3A 0G4, CanadaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaInstitute of Suzhou Biobank, Suzhou Center for Disease Prevention and Control, Suzhou 215007, ChinaSchool of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, ChinaProgressive loss and dysfunction of islet β-cells has not yet been solved in the treatment of diabetes. Regenerating protein (Reg) has been identified as a trophic factor which is demonstrated to be associated with pancreatic tissue regeneration. We previously produced recombinant Reg3α protein (rReg3α) and proved that it protects against acute pancreatitis in mice. Whether rReg3α protects islet β-cells in diabetes has been elusive. In the present study, rReg3α stimulated MIN6 cell proliferation and resisted STZ-caused cell death. The protective effect of rReg3α was also found in mouse primary islets. In BALB/c mice, rReg3α administration largely alleviated STZ-induced diabetes by the preservation of β-cell mass. The protective mechanism could be attributed to Akt/Bcl-2/-xL activation and GRP78 upregulation. Scattered insulin-expressing cells and clusters with small size, low insulin density, and exocrine distribution were observed and considered to be neogenic. In isolated acinar cells with wheat germ agglutinin (WGA) labeling, rReg3α treatment generated insulin-producing cells through Stat3/Ngn3 signaling, but these cells were not fully functional in response to glucose stimulation. Our results demonstrated that rReg3α resists STZ-induced β-cell death and promotes β-cell regeneration. rReg3α could serve as a potential drug for β-cell maintenance in anti-diabetic treatment.https://www.mdpi.com/1422-0067/23/18/10584regenerating proteindiabetesthe isletsβ-cell regenerationGRP78 |
| spellingShingle | Luting Yu Liang Li Junli Liu Hao Sun Xiang Li Hanyu Xiao Martin Omondi Alfred Min Wang Xuri Wu Yan Gao Chen Luo Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration International Journal of Molecular Sciences regenerating protein diabetes the islets β-cell regeneration GRP78 |
| title | Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration |
| title_full | Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration |
| title_fullStr | Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration |
| title_full_unstemmed | Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration |
| title_short | Recombinant Reg3α Prevents Islet β-Cell Apoptosis and Promotes β-Cell Regeneration |
| title_sort | recombinant reg3α prevents islet β cell apoptosis and promotes β cell regeneration |
| topic | regenerating protein diabetes the islets β-cell regeneration GRP78 |
| url | https://www.mdpi.com/1422-0067/23/18/10584 |
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