Prevention of autoimmune diabetes and induction of β-cell proliferation in NOD mice by hyperbaric oxygen therapy

Gaetano Faleo, Carmen Fotino, Nicola Bocca, R. Damaris Molano, Elsie Zahr-Akrawi, Judith Molina, Susana Villate, Oliver Umland, Jay S. Skyler, Allison L. Bayer, Camillo Ricordi, Antonello Pileggi

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1769-1778
Number of pages10
JournalDiabetes
Volume61
Issue number7
DOIs
StatePublished - Jul 1 2012

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Faleo, G., Fotino, C., Bocca, N., Molano, R. D., Zahr-Akrawi, E., Molina, J., Villate, S., Umland, O., Skyler, J. S., Bayer, A. L., Ricordi, C., & Pileggi, A. (2012). Prevention of autoimmune diabetes and induction of β-cell proliferation in NOD mice by hyperbaric oxygen therapy. Diabetes, 61(7), 1769-1778. https://doi.org/10.2337/db11-0516