Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation
Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder accompanied by high blood glucose, insulin resistance, and relative insulin deficiency. Endoplasmic reticulum (ER) stress induced by high glucose and free fatty acids has been suggested as one of the main causes of β-...
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MDPI AG
2019-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/4/368 |
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| author | Younghay Lee Sun-Hye Shin Kyung-Ah Cho Yu-Hee Kim So-Youn Woo Han Su Kim Sung-Chul Jung Inho Jo Hee-Sook Jun Woo-Jae Park Joo-Won Park Kyung-Ha Ryu |
| author_facet | Younghay Lee Sun-Hye Shin Kyung-Ah Cho Yu-Hee Kim So-Youn Woo Han Su Kim Sung-Chul Jung Inho Jo Hee-Sook Jun Woo-Jae Park Joo-Won Park Kyung-Ha Ryu |
| author_sort | Younghay Lee |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder accompanied by high blood glucose, insulin resistance, and relative insulin deficiency. Endoplasmic reticulum (ER) stress induced by high glucose and free fatty acids has been suggested as one of the main causes of β-cell dysfunction and death in T2DM. Stem cell-derived insulin-secreting cells were recently suggested as a novel therapy for diabetes. In the present study, we demonstrate the therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) to treat high-fat diet (HFD)-induced T2DM. To explore whether TMSC administration can alleviate T2DM, TMSCs were intraperitoneally injected in HFD-induced T2DM mice once every 2 weeks. TMSC injection markedly improved glucose tolerance and glucose-stimulated insulin secretion and prevented HFD-induced pancreatic β-cell hypertrophy and cell death. In addition, TMSC injection relieved the ER-stress response and preserved gene expression related to glucose sensing and insulin secretion. Moreover, administration of TMSC-derived conditioned medium induced similar therapeutic outcomes, suggesting paracrine effects. Finally, proteomic analysis revealed high secretion of insulin-like growth factor-binding protein 5 by TMSCs, and its expression was critical for the protective effects of TMSCs against HFD-induced glucose intolerance and ER-stress response in pancreatic islets. TMSC administration can alleviate HFD-induced-T2DM via preserving pancreatic islets and their function. These results provide novel evidence of TMSCs as an ER-stress modulator that may be a novel, alternative cell therapy for T2DM. |
| first_indexed | 2024-03-12T09:47:04Z |
| format | Article |
| id | doaj.art-5292351660e3421f9ade64e1d15c39d6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T09:47:04Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5292351660e3421f9ade64e1d15c39d62023-09-02T12:50:21ZengMDPI AGCells2073-44092019-04-018436810.3390/cells8040368cells8040368Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress ModulationYounghay Lee0Sun-Hye Shin1Kyung-Ah Cho2Yu-Hee Kim3So-Youn Woo4Han Su Kim5Sung-Chul Jung6Inho Jo7Hee-Sook Jun8Woo-Jae Park9Joo-Won Park10Kyung-Ha Ryu11Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Otolaryngology, College of Medicine, Ewha Womans University, Seoul 07985, KoreaDepartment of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, KoreaCollege of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21999, KoreaDepartment of Biochemistry, College of Medicine, Gachon University, Incheon 21999, KoreaDepartment of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Pediatrics, College of Medicine, Ewha Womans University, Seoul 07804, KoreaType 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder accompanied by high blood glucose, insulin resistance, and relative insulin deficiency. Endoplasmic reticulum (ER) stress induced by high glucose and free fatty acids has been suggested as one of the main causes of β-cell dysfunction and death in T2DM. Stem cell-derived insulin-secreting cells were recently suggested as a novel therapy for diabetes. In the present study, we demonstrate the therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) to treat high-fat diet (HFD)-induced T2DM. To explore whether TMSC administration can alleviate T2DM, TMSCs were intraperitoneally injected in HFD-induced T2DM mice once every 2 weeks. TMSC injection markedly improved glucose tolerance and glucose-stimulated insulin secretion and prevented HFD-induced pancreatic β-cell hypertrophy and cell death. In addition, TMSC injection relieved the ER-stress response and preserved gene expression related to glucose sensing and insulin secretion. Moreover, administration of TMSC-derived conditioned medium induced similar therapeutic outcomes, suggesting paracrine effects. Finally, proteomic analysis revealed high secretion of insulin-like growth factor-binding protein 5 by TMSCs, and its expression was critical for the protective effects of TMSCs against HFD-induced glucose intolerance and ER-stress response in pancreatic islets. TMSC administration can alleviate HFD-induced-T2DM via preserving pancreatic islets and their function. These results provide novel evidence of TMSCs as an ER-stress modulator that may be a novel, alternative cell therapy for T2DM.https://www.mdpi.com/2073-4409/8/4/368type 2 diabetes mellitustonsilmesenchymal stem cellpancreasinsulin-like growth factor-binding protein 5 |
| spellingShingle | Younghay Lee Sun-Hye Shin Kyung-Ah Cho Yu-Hee Kim So-Youn Woo Han Su Kim Sung-Chul Jung Inho Jo Hee-Sook Jun Woo-Jae Park Joo-Won Park Kyung-Ha Ryu Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation Cells type 2 diabetes mellitus tonsil mesenchymal stem cell pancreas insulin-like growth factor-binding protein 5 |
| title | Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation |
| title_full | Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation |
| title_fullStr | Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation |
| title_full_unstemmed | Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation |
| title_short | Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation |
| title_sort | administration of tonsil derived mesenchymal stem cells improves glucose tolerance in high fat diet induced diabetic mice via insulin like growth factor binding protein 5 mediated endoplasmic reticulum stress modulation |
| topic | type 2 diabetes mellitus tonsil mesenchymal stem cell pancreas insulin-like growth factor-binding protein 5 |
| url | https://www.mdpi.com/2073-4409/8/4/368 |
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