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    Research reveals insulin-producing beta cells may change function in diabetes

    yoly
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    Research reveals insulin-producing beta cells may change function in diabetes Empty Research reveals insulin-producing beta cells may change function in diabetes

    Post by yoly on Sun May 19 2019, 12:52

    Cellular stressors may alter islet hormone cell proportions by moderation of alternative splicing patterns
    complete study on link

    https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddz094/5487670

    Abstract

    Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns of key genes in EndoC-βH1 human beta cells. Genes encoding islet hormones [somatostatin (SST), insulin (INS), Glucagon (GCG)], differentiation markers [Forkhead box O1 (FOXO1), Paired box 6, SRY box 9, NK6 Homeobox 1, NK6 Homeobox 2] and cell stress markers (DNA damage inducible transcript 3, FOXO1) were dysregulated in stressed EndoC-βH1 cells, as were some serine arginine rich splicing factor splicing activator and heterogeneous ribonucleoprotein particle inhibitor genes. Whole transcriptome analysis of primary T2D islets and matched controls demonstrated dysregulated splicing for ~25% of splicing events, of which genes themselves involved in messenger ribonucleic acid processing and regulation of gene expression comprised the largest group. Approximately 5% of EndoC-βH1 cells exposed to these factors gained SST positivity in vitro. An increased area of SST staining was also observed ex vivo in pancreas sections recovered at autopsy from donors with type 1 diabetes (T1D) or T2D (9.3% for T1D and 3% for T2D, respectively compared with 1% in controls). Removal of the stressful stimulus or treatment with the AKT Serine/Threonine kinase inhibitor SH-6 restored splicing factor expression and reversed both hormone staining effects and patterns of gene expression. This suggests that reversible changes in hormone expression may occur during exposure to diabetomimetic cellular stressors, which may be mediated by changes in splicing regulation.

    Jan1
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    Research reveals insulin-producing beta cells may change function in diabetes Empty Re: Research reveals insulin-producing beta cells may change function in diabetes

    Post by Jan1 on Sun May 19 2019, 17:42

    Many thanks Yoly.
    I used your link and discovered a long and detailed read  Smile 

    All the best Jan

    https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddz094/5487670

      Current date/time is Wed Jun 26 2019, 11:50