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c-Myc directly induces both impaired insulin secretion and loss of β-cell mass, independently of hyperglycemia in vivo
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Cheung, Linda, Zervou, Sevasti I., Mattsson, Göran, Abouna, Sylvie, Zhou, Luxian, Ifandi, Vasiliki, Pelengaris, Stella and Khan, Michael. (2010) c-Myc directly induces both impaired insulin secretion and loss of β-cell mass, independently of hyperglycemia in vivo. Islets, Vol.2 (No.1). pp. 37-45. ISSN 1938-2014
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Official URL: http://dx.doi.org/10.4161/isl.2.1.10196
Abstract
c-Myc (Myc) is a mediator of glucotoxicity but could also independently compromise beta-cell survival and function. We have shown that after Myc activation in adult beta-cells in vivo, apoptosis is preceded by hyperglycemia, suggesting glucotoxicity might contribute to Myc-induced apoptosis. To address this question conditional Myc was activated in beta-cells of adult plns-c-MycER(TAM) mice in vivo in the presence or absence of various glucose-lowering treatments, including exogenous insulin and prior to transplantation with wild-type islets. Changes in blood glucose levels were subsequently correlated with changes in beta-cell mass and markers of function/differentiation. Activation of c-Myc resulted in reduced insulin secretion, hyperglycemia and loss of beta-cell differentiation, followed by reduction in mass. Glucose-lowering interventions did not prevent loss of beta-cells. Therefore, Myc can cause diabetes by direct effects on beta-cell apoptosis even in the absence of potentially confounding secondary hyperglycemia. Moreover, as loss of beta-cell differentiation/function and hyperglycemia are not prevented by preventing beta-cell apoptosis, we conclude that Myc might contribute to the pathogenesis of diabetes by directly coupling cell cycle entry and beta-cell failure through two distinct pathways.
| Item Type: | Journal Article |
|---|---|
| Divisions: | Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010) Faculty of Science > Life Sciences (2010- ) |
| Journal or Publication Title: | Islets |
| Publisher: | Landes Bioscience |
| ISSN: | 1938-2014 |
| Date: | 2010 |
| Volume: | Vol.2 |
| Number: | No.1 |
| Page Range: | pp. 37-45 |
| Identification Number: | 10.4161/isl.2.1.10196 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| URI: | http://wrap.warwick.ac.uk/id/eprint/41462 |
Data sourced from Thomson Reuters' Web of Knowledge
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