Prevention of Autoimmune Diabetes and Induction of β-Cell Proliferation in NOD Mice by Hyperbaric Oxygen Therapy
- Gaetano Faleo1,
- Carmen Fotino1,
- Nicola Bocca1,
- R. Damaris Molano1,
- Elsie Zahr-Akrawi1,
- Judith Molina1,
- Susana Villate1,
- Oliver Umland1,
- Jay S. Skyler1,2,
- Allison L. Bayer1,3,
- Camillo Ricordi1,2,3,4,5⇓ and
- Antonello Pileggi1,2,4,5⇓
- 1Diabetes Research Institute, Cell Transplant Center, University of Miami, Miami, Florida
- 2Department of Medicine, University of Miami, Miami, Florida
- 3Department of Microbiology and Immunology, University of Miami, Miami, Florida
- 4DeWitt Daughtry Family Department of Surgery, University of Miami, Miami, Florida
- 5Department of Biomedical Engineering, University of Miami, Miami, Florida
- Corresponding author: Antonello Pileggi, .
G.F., C.F., and N.B. contributed equally to this study.
We evaluated the effects of hyperbaric oxygen therapy (HOT) on autoimmune diabetes development in nonobese diabetic (NOD) mice. Animals received no treatment or daily 60-min HOT 100% oxygen (HOT-100%) at 2.0 atmospheres absolute and were monitored for diabetes onset, insulitis, infiltrating cells, immune cell function, and β-cell apoptosis and proliferation. Cyclophosphamide-induced diabetes onset was reduced from 85.3% in controls to 48% after HOT-100% (P < 0.005) and paralleled by lower insulitis. Spontaneous diabetes incidence reduced from 85% in controls to 65% in HOT-100% (P = 0.01). Prediabetic mice receiving HOT-100% showed lower insulitis scores, reduced T-cell proliferation upon stimulation in vitro (P < 0.03), increased CD62L expression in T cells (P < 0.04), reduced costimulation markers (CD40, DC80, and CD86), and reduced major histocompatibility complex class II expression in dendritic cells (DCs) (P < 0.025), compared with controls. After autoimmunity was established, HOT was less effective. HOT-100% yielded reduced apoptosis (transferase-mediated dUTP nick-end labeling-positive insulin-positive cells; P < 0.01) and increased proliferation (bromodeoxyuridine incorporation; P < 0.001) of insulin-positive cells compared with controls. HOT reduces autoimmune diabetes incidence in NOD mice via increased resting T cells and reduced activation of DCs with preservation of β-cell mass resulting from decreased apoptosis and increased proliferation. The safety profile and noninvasiveness makes HOT an appealing adjuvant therapy for diabetes prevention and intervention trials.
- Received April 15, 2011.
- Accepted March 4, 2012.
- © 2012 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.