Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow-bone marrow transplantation plus concurrent thymic transplantation

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

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)414-423
Number of pages10
JournalJournal of Autoimmunity
Volume35
Issue number4
DOIs
StatePublished - Dec 2010

Keywords

  • Db/db/ mice
  • Intra-bone marrow-bone marrow transplantation
  • Thymic transplantation
  • Type 2 diabetes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Li, M., Abraham, N. G., Vanella, L., Zhang, Y., Inaba, M., Hosaka, N., Hoshino, S. I., Shi, M., Ambrosini, Y. M., Gershwin, M. E., & Ikehara, S. (2010). Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow-bone marrow transplantation plus concurrent thymic transplantation. Journal of Autoimmunity, 35(4), 414-423. https://doi.org/10.1016/j.jaut.2010.09.001