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Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes – published online 24/07/2020

Christin Krause, Cathleen Geißler, Heidi Tackenberg, Alexander T. El Gammal, Stefan Wolter, Joachim Spranger, Oliver Mann, Hendrik Lehnert, Henriette Kirchner

Epigenetic regulation of gene expression is altered in type 2 diabetes. However, epigenetic regulation of insulin signalling in key metabolic tissues in type 2 diabetes is largely unknown. In this issue, Krause et al (https://doi.org/10.1007/s00125-020-05212-6) analysed the epigenetic gene regulation of IRS2, which encodes a crucial mediator of insulin signal transduction, in liver biopsies of obese individuals with and without type 2 diabetes. They found that hepatic expression of IRS2 is decreased in type 2 diabetes, which is accompanied by decreased intronic DNA methylation and enhanced binding of two transcriptional repressors. They also report that the microRNA let-7e-5p is increased in the liver in diabetes, correlates with the decreased IRS2expression, and might represent a complementary mechanism of IRS2 regulation. The authors conclude that these findings contribute to an improved understanding of dysregulated pathways in the liver of individuals with type 2 diabetes and illustrate the complexity and multifactorial nature of mechanisms involved in the regulation of glucose homeostasis.

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