Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: Role of IFNβ

R. Planas, A. Alba, J. Carrillo, M. C. Puertas, R. Ampudia, X. Pastor, H. Okamoto, S. Takasawa, W. Gurr, R. Pujol-Borrell, J. Verdaguer, M. Vives-Pi

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29 Citations (Scopus)

Abstract

Aims/hypothesis: The expression of IFNβ in beta cells results in accelerated type 1 diabetes. The REG family of beta cell proliferation factors have been described as autoantigens in autoimmune diabetes. The aim of this study was to determine the effect of IFNβ on Reg expression, and the implications of this in terms of autoimmunity. Methods: Reg gene expression was determined in islets from non-obese diabetic (NOD) RIP-HuIFNβ mice by cDNA microarray, quantitative real-time PCR and immunohistochemistry. The effect of IFNβ on Reg1 and Reg2 expression was assessed in the NOD insulinoma cell line NIT-1. IL-6, known to induce Reg expression, was measured in the insulitis microenvironment. Morphological studies were carried out to determine islet enlargement in this model. Results: Reg2 was upregulated in islets from the NOD RIP-HuIFNβ mice at the onset of the autoimmune attack. IFNβ upregulates Reg1 and Reg2 genes in NIT-1 cells. The expression of Il6 was increased in islets from transgenic mice and in NIT-1 cells exposed to HuIFNβ. Moreover, islets from transgenic mice were enlarged compared with those from wild-type mice. Conclusions/interpretation: Reg overexpression correlates well with the acceleration of diabetes in this model. The upregulation of Reg suggests that islets try to improve hyperglycaemia by regenerating the cells lost in the autoimmune attack. Reg expression is regulated by several factors such as inflammation. Therefore, the overexpression of an IFNβ-induced autoantigen (REG) in the islets during inflammation might contribute to the premature onset of diabetes.

Original languageEnglish
Pages (from-to)2379-2387
Number of pages9
JournalDiabetologia
Volume49
Issue number10
DOIs
Publication statusPublished - 2006 Oct

Keywords

  • Diabetes
  • IFNβ
  • Islets
  • NOD mice
  • REG
  • Regenerating gene

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Planas, R., Alba, A., Carrillo, J., Puertas, M. C., Ampudia, R., Pastor, X., Okamoto, H., Takasawa, S., Gurr, W., Pujol-Borrell, R., Verdaguer, J., & Vives-Pi, M. (2006). Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: Role of IFNβ. Diabetologia, 49(10), 2379-2387. https://doi.org/10.1007/s00125-006-0365-6