Document Detail


Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow--bone marrow transplantation plus concurrent thymic transplantation.
MedLine Citation:
PMID:  20884174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of autoimmunity     Volume:  35     ISSN:  1095-9157     ISO Abbreviation:  J. Autoimmun.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-25     Completed Date:  2011-05-23     Revised Date:  2012-04-09    
Medline Journal Info:
Nlm Unique ID:  8812164     Medline TA:  J Autoimmun     Country:  England    
Other Details:
Languages:  eng     Pagination:  414-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka 570-8506, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adiponectin / 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:
DK068134/DK/NIDDK NIH HHS; HL34300/HL/NHLBI NIH HHS; HL55601/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adiponectin; 0/Adipoq protein, mouse; 0/Blood Glucose; 0/Interleukin-1beta; 0/Interleukin-6; 0/Receptors, Leptin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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