| Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow--bone marrow transplantation plus concurrent thymic transplantation. | |
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MedLine Citation:
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PMID: 20884174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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There is increasing evidence that both autoimmune and autoinflammatory mechanisms are involved in the development of not only type 1 diabetes mellitus (T1 DM), but also type 2 diabetes mellitus (T2 DM). Our laboratory has focused on this concept, and in earlier efforts replaced the bone marrow cells (BMCs) of leptin receptor-deficient (db/db) mice, an animal model of T2DM, with those of normal C57BL/6 (B6) mice by IBM-BMT. However, the outcome was poor due to incomplete recovery of T cell function. Therefore, we hypothesized that intra-bone marrow-bone marrow transplantation plus thymus transplantation (IBM-BMT + TT) could be used to treat T2 DM by normalizing the T cell imbalance. Hence we addressed this issue by using such dual transplantation and demonstrate herein that seven weeks later, recipient db/db mice manifested improved body weight, reduced levels of blood glucose, and a reduction of plasma IL-6 and IL-1β. More importantly, this treatment regimen showed normal CD4/CD8 ratios, and increased plasma adiponectin levels, insulin sensitivity, and the number of insulin-producing cells. Furthermore, the expression of pancreatic pAKT, pLKB1, pAMPK and HO-1 was increased in the mice treated with IBM-BMT + TT. Our data show that IBM-BMT + TT treatment normalizes T cell subsets, cytokine imbalance and insulin sensitivity in the db/db mouse, suggesting that IBM-BMT + TT is a viable therapeutic option in the treatment of T2 DM. |
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Authors:
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Ming Li; Nader G Abraham; Luca Vanella; Yuming Zhang; Muneo Inaba; Naoki Hosaka; Sho-Ichi Hoshino; Ming Shi; Yoko Miyamoto Ambrosini; M Eric Gershwin; Susumu Ikehara |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of autoimmunity Volume: 35 ISSN: 1095-9157 ISO Abbreviation: J. Autoimmun. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-10-25 Completed Date: 2011-05-23 Revised Date: 2012-04-09 |
Medline Journal Info:
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Nlm Unique ID: 8812164 Medline TA: J Autoimmun Country: England |
Other Details:
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Languages: eng Pagination: 414-23 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka 570-8506, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adiponectin
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blood Animals Blood Glucose / biosynthesis, genetics Bone Marrow Transplantation Diabetes Mellitus, Type 2 / blood, immunology*, therapy* Disease Models, Animal Gene Expression Regulation Humans Immunotherapy* Insulin-Secreting Cells / pathology Interleukin-1beta / biosynthesis, genetics Interleukin-6 / biosynthesis, genetics Mice Mice, Inbred C57BL Mice, Mutant Strains Receptors, Leptin / deficiency T-Lymphocytes / immunology, metabolism*, pathology Thymus Gland / transplantation* |
| Grant Support | |
ID/Acronym/Agency:
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DK068134/DK/NIDDK NIH HHS; HL34300/HL/NHLBI NIH HHS; HL55601/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Adipoq protein, mouse; 0/Blood Glucose; 0/Interleukin-1beta; 0/Interleukin-6; 0/Receptors, Leptin |
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