PMID- 20884174
OWN - NLM
STAT- MEDLINE
DCOM- 20110523
LR  - 20211020
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 35
IP  - 4
DP  - 2010 Dec
TI  - Successful modulation of type 2 diabetes in db/db mice with intra-bone 
      marrow--bone marrow transplantation plus concurrent thymic transplantation.
PG  - 414-23
LID - 10.1016/j.jaut.2010.09.001 [doi]
AB  - 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-1beta. 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.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Li, Ming
AU  - Li M
AD  - Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, 
      Osaka 570-8506, Japan.
FAU - Abraham, Nader G
AU  - Abraham NG
FAU - Vanella, Luca
AU  - Vanella L
FAU - Zhang, Yuming
AU  - Zhang Y
FAU - Inaba, Muneo
AU  - Inaba M
FAU - Hosaka, Naoki
AU  - Hosaka N
FAU - Hoshino, Sho-Ichi
AU  - Hoshino S
FAU - Shi, Ming
AU  - Shi M
FAU - Ambrosini, Yoko Miyamoto
AU  - Ambrosini YM
FAU - Gershwin, M Eric
AU  - Gershwin ME
FAU - Ikehara, Susumu
AU  - Ikehara S
LA  - eng
GR  - R01 DK068134/DK/NIDDK NIH HHS/United States
GR  - P01 HL034300/HL/NHLBI NIH HHS/United States
GR  - HL34300/HL/NHLBI NIH HHS/United States
GR  - HL55601/HL/NHLBI NIH HHS/United States
GR  - DK068134/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - 0 (Adiponectin)
RN  - 0 (Adipoq protein, mouse)
RN  - 0 (Blood Glucose)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Leptin)
SB  - IM
MH  - Adiponectin/blood
MH  - Animals
MH  - Blood Glucose/biosynthesis/genetics
MH  - Bone Marrow Transplantation
MH  - Diabetes Mellitus, Type 2/blood/*immunology/*therapy
MH  - Disease Models, Animal
MH  - Gene Expression Regulation
MH  - Humans
MH  - *Immunotherapy
MH  - Insulin-Secreting Cells/pathology
MH  - Interleukin-1beta/biosynthesis/genetics
MH  - Interleukin-6/biosynthesis/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Receptors, Leptin/deficiency
MH  - T-Lymphocytes/immunology/*metabolism/pathology
MH  - Thymus Gland/*transplantation
PMC - PMC5553687
MID - NIHMS889059
EDAT- 2010/10/05 06:00
MHDA- 2011/05/24 06:00
PMCR- 2017/08/11
CRDT- 2010/10/02 06:00
PHST- 2010/08/14 00:00 [received]
PHST- 2010/09/02 00:00 [revised]
PHST- 2010/09/03 00:00 [accepted]
PHST- 2010/10/02 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/05/24 06:00 [medline]
PHST- 2017/08/11 00:00 [pmc-release]
AID - S0896-8411(10)00100-9 [pii]
AID - 10.1016/j.jaut.2010.09.001 [doi]
PST - ppublish
SO  - J Autoimmun. 2010 Dec;35(4):414-23. doi: 10.1016/j.jaut.2010.09.001.