Glucose tolerance is associated with differential expression of microRNAs in skeletal muscle: results from studies of twins with and without type 2 diabetesReportar como inadecuado


Glucose tolerance is associated with differential expression of microRNAs in skeletal muscle: results from studies of twins with and without type 2 diabetes


Glucose tolerance is associated with differential expression of microRNAs in skeletal muscle: results from studies of twins with and without type 2 diabetes - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Publication Date: 2014-11-19

Journal Title: Diabetologia

Publisher: Springer

Volume: 58

Issue: 2

Pages: 363-373

Language: English

Type: Article

Metadata: Show full item record

Citation: Bork-Jensen, J., Scheele, C., Christophersen, D. V., Nilsson, E., Friedrichsen, M., Fernandez-Twinn, D. S., Grunnet, L. G., et al. (2014). Glucose tolerance is associated with differential expression of microRNAs in skeletal muscle: results from studies of twins with and without type 2 diabetes. Diabetologia, 58 (2), 363-373.

Description: This is the final version of the article. It was first published by Springer at http://link.springer.com/article/10.1007%2Fs00125-014-3434-2

Abstract: Aims/hypothesis: We aimed to identify microRNAs (miRNAs) associated with type 2 diabetes and risk of developing the disease in skeletal muscle biopsies from phenotypically well-characterised twins. Methods: We measured muscle miRNA levels in monozygotic (MZ) twins discordant for type 2 diabetes using arrays. Further investigations of selected miRNAs included target prediction, pathway analysis, silencing in cells and association analyses in a separate cohort of 164 non-diabetic MZ and dizygotic twins. The effects of elevated glucose and insulin levels on miRNA expression were examined, and the effect of low birthweight (LBW) was studied in rats. Results: We identified 20 miRNAs that were downregulated in MZ twins with diabetes compared with their non-diabetic co-twins. Differences for members of the miR-15 family (miR-15b and miR-16) were the most statistically significant, and these miRNAs were predicted to influence insulin signalling. Indeed, miR-15b and miR-16 levels were associated with levels of key insulin signalling proteins, miR-15b was associated with the insulin receptor in non-diabetic twins and knockdown of miR-15b/miR-16 in myocytes changed the levels of insulin signalling proteins. LBW in twins and undernutrition during pregnancy in rats were, in contrast to overt type 2 diabetes, associated with increased expression of miR-15b and/or miR-16. Elevated glucose and insulin suppressed miR-16 expression in vitro. Conclusions: Type 2 diabetes is associated with non-genetic downregulation of several miRNAs in skeletal muscle including miR-15b and miR-16, potentially targeting insulin signalling. The paradoxical findings in twins with overt diabetes and twins at increased risk of the disease underscore the complexity of the regulation of muscle insulin signalling in glucose homeostasis.

Sponsorship: JB-J was supported by a grant from the Danish PhD School for Molecular Metabolism. The study was supported by grants from the Danish Medical Research Council, the Danish Strategic Research Council. The Novo Nordisk Foundation, the Danish Ministry of Science, Technology and Innovation. DSF-T was supported by the Biotechnology and Biological Sciences Research Council project grant BB/F-15364/1. SEO is a British Heart Foundation Senior Fellow (FS/09/029/27902).

Identifiers:

This record's URL: http://dx.doi.org/10.1007/s00125-014-3434-2http://www.repository.cam.ac.uk/handle/1810/247077

Rights: Attribution 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by/2.0/uk/





Autor: Bork-Jensen, JetteScheele, CamillaChristophersen, Daniel V.Nilsson, EmmaFriedrichsen, MartinFernandez-Twinn, Denise S.Grunnet, Lou

Fuente: https://www.repository.cam.ac.uk/handle/1810/247077



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