Differential expression of novel adiponectin receptor-1 transcripts in skeletal muscle of subjects with normal glucose tolerance and type 2 diabetes.
Objective: Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiologi...
| Publicado en: | Diabetes Vol. 60; no. 3; pp. 936 - 947 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
American Diabetes Association
Mar2011
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104834784&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104834784 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00121797 1G6 jtl: Diabetes issn: 00121797 maglogo: N pubinfo: dt: Mar2011 vid: 60 iid: 3 pid: 1367 pub: American Diabetes Association place: Arlington, Virginia artinfo: ui: 104834784 NLM21289205 2010967117 10.2337/db09-0532 NLM21289205 PMC3046855 104834784 ppf: 936 ppct: 11 formats: tig: atl: Differential expression of novel adiponectin receptor-1 transcripts in skeletal muscle of subjects with normal glucose tolerance and type 2 diabetes. aug: au: Ashwal R Hemi R Tirosh A Gordin R Yissachar E Cohen-Dayag A Rosenberg A Karasik A Blüher M Kanety H Ashwal, Reut Hemi, Rina Tirosh, Amir Gordin, Reut Yissachar, Eleanor Cohen-Dayag, Anat Rosenberg, Avi Karasik, Avraham Blüher, Matthias Kanety, Hannah affil: Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, Israel sug: subj: Diabetes Mellitus, Type 2 Metabolism Glucose Metabolism Muscle, Skeletal Metabolism Receptors, Cell Surface Metabolism RNA Adult Blotting, Western Cells Diabetes Mellitus, Type 2 Genes Human Insulin Resistance Muscle, Skeletal Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction Adult: 19-44 years ab: Objective: Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiological states.Research Design and Methods: AdipoR1 5'UTR mRNA transcripts, predicted from bioinformatics data, were evaluated in fetal and adult human tissues. Expression and function of the identified transcripts were assessed in cultured human skeletal muscle cells and in muscle biopsies obtained from individuals with normal glucose tolerance (NGT) and type 2 diabetes (n = 49).Results: Screening of potential AdipoR1 5'UTR splice variants revealed a novel highly abundant muscle transcript (R1T3) in addition to the previously described transcript (R1T1). Unlike R1T1, R1T3 expression was significantly increased during fetal development and myogenesis, paralleled with increased AdipoR1 protein expression. The 5'UTR of R1T3 was found to contain upstream open reading frames that repress translation of downstream coding sequences. Conversely, AdipoR1 3'UTR was associated with enhanced translation efficiency during myoblast-myotube differentiation. A marked reduction in muscle expression of R1T3, R1T1, and R1T3-to-R1T1 ratio was observed in individuals with type 2 diabetes compared with expression levels of NGT subjects, paralleled with decreased expression of the differentiation marker myogenin. Among NGT subjects, R1T3 expression was positively correlated with insulin sensitivity.Conclusions: These results indicate that AdipoR1 receptor expression in human skeletal muscle is subjected to posttranscriptional regulation, including alternative splicing and translational control. These mechanisms play an important role during myogenesis and may be important for whole-body insulin sensitivity. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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