IL-13 improves beta-cell survival and protects against IL-1beta-induced beta-cell death

Objectives: IL-13 is a cytokine classically produced by anti-inflammatory T-helper-2 lymphocytes; it is decreased in the circulation of type 2 diabetic patients and impacts positively on liver and skeletal muscle. Although IL-13 can exert positive effects on beta-cell lines, its impact and mode of action on primary beta-cell function and survival remain largely unexplored. Methods: Beta-cells were cultured for 48 h in the presence of IL-13 alone or in combination with IL-1 beta or cytokine cocktail (IL-1 beta, IFN gamma, TNF alpha). Results: IL-13 protected human and rat beta-cells against cytokine induced death. However, IL-beta was unable to protect from IL-1 beta impaired glucose stimulated insulin secretion and did not influence NFkB nuclear relocalization induced by IL-1 beta. IL-13 induced phosphorylation of Akt, increased IRS2 protein expression and counteracted the IL-1 beta induced regulation of several beta-cell stress response genes. Conclusions: The prosurvival effects of IL-13 thus appear to be mediated through IRS2/Akt signaling with NF kappa B independent regulation of gene expression. In addition to previously documented beneficial effects on insulin target tissues, these data suggest that IL-13 may be useful for treatment of type 2 diabetes by preserving beta-cell mass or slowing its rate of decline. (C) 2015 The Authors. Published by Elsevier GmbH.