Home > Articles > Published articles > Insulin-like growth factor 2 overexpression induces β-Cell dysfunction and increases beta-cell susceptibility to damage |
Date: | 2015 |
Abstract: | The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function. |
Grants: | Ministerio de Economía y Competitividad SAF2008-00962 Ministerio de Economía y Competitividad SAF2011-24698 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-224 Ministerio de Economía y Competitividad JCI2010-06388 |
Rights: | Tots els drets reservats. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Published in: | Journal of biological chemistry, Vol. 290 Núm. 27 (Juliol 2015) , p. 16772-16785, ISSN 1083-351X |
15 p, 3.3 MB |