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

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

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

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Hyperbaric Oxygenation
Inbred NOD Mouse
Type 1 Diabetes Mellitus
Cell Proliferation
Apoptosis
T-Lymphocytes
Dendritic Cells
Insulin
Incidence
Bromodeoxyuridine
Transferases
Major Histocompatibility Complex
Autoimmunity
Atmosphere
Cyclophosphamide
Oxygen
Safety

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Faleo, G., Fotino, C., Bocca, N., Molano, R., Zahr-Akrawi, E., Molina, J., ... 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

Prevention of autoimmune diabetes and induction of β-cell proliferation in NOD mice by hyperbaric oxygen therapy. / Faleo, Gaetano; Fotino, Carmen; Bocca, Nicola; Molano, Ruth; Zahr-Akrawi, Elsie; Molina, Judith; Villate, Susana; Umland, Oliver; Skyler, Jay S; Bayer, Allison L; Ricordi, Camillo; Pileggi, Antonello.

In: Diabetes, Vol. 61, No. 7, 01.07.2012, p. 1769-1778.

Research output: Contribution to journalArticle

Faleo, G, Fotino, C, Bocca, N, Molano, R, Zahr-Akrawi, E, Molina, J, Villate, S, Umland, O, Skyler, JS, Bayer, AL, Ricordi, C & Pileggi, A 2012, 'Prevention of autoimmune diabetes and induction of β-cell proliferation in NOD mice by hyperbaric oxygen therapy', Diabetes, vol. 61, no. 7, pp. 1769-1778. https://doi.org/10.2337/db11-0516
Faleo, Gaetano ; Fotino, Carmen ; Bocca, Nicola ; Molano, Ruth ; Zahr-Akrawi, Elsie ; Molina, Judith ; Villate, Susana ; Umland, Oliver ; Skyler, Jay S ; Bayer, Allison L ; Ricordi, Camillo ; Pileggi, Antonello. / Prevention of autoimmune diabetes and induction of β-cell proliferation in NOD mice by hyperbaric oxygen therapy. In: Diabetes. 2012 ; Vol. 61, No. 7. pp. 1769-1778.
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