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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
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
Authors
Lee, YounghayShin, Sun-HyeCho, Kyung-AhKim, Yu-HeeWoo, So-YounKim, Han SuJung, Sung-ChulJo, InhoJun, Hee-SookPark, Woo-JaePark, Joo-WonRyu, Kyung-Ha
Ewha Authors
유경하우소연김한수정성철조인호박주원김유희조경아
SCOPUS Author ID
유경하scopus; 우소연scopus; 김한수scopus; 정성철scopus; 조인호scopus; 박주원scopus; 김유희scopus; 조경아scopus
Issue Date
2019
Journal Title
CELLS
ISSN
2073-4409JCR Link
Citation
CELLS vol. 8, no. 4
Keywords
type 2 diabetes mellitustonsilmesenchymal stem cellpancreasinsulin-like growth factor-binding protein 5
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
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 -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 -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.
DOI
10.3390/cells8040368
Appears in Collections:
의과대학 > 의학과 > Journal papers
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