title: Differential expression of novel adiponectin receptor-1 transcripts in skeletal muscle of subjects with normal glucose tolerance and type 2 diabetes.
abstract: 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.
  
  
  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.
authors.affiliation: Institute of Endocrinology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Reut
authors.initials: R
authors.lastname: Ashwal
authors.forename: Rina
authors.initials: R
authors.lastname: Hemi
authors.forename: Amir
authors.initials: A
authors.lastname: Tirosh
authors.forename: Reut
authors.initials: R
authors.lastname: Gordin
authors.forename: Eleanor
authors.initials: E
authors.lastname: Yissachar
authors.forename: Anat
authors.initials: A
authors.lastname: Cohen-Dayag
authors.forename: Avi
authors.initials: A
authors.lastname: Rosenberg
authors.forename: Avraham
authors.initials: A
authors.lastname: Karasik
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Hannah
authors.initials: H
authors.lastname: Kanety
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020121:5' Untranslated Regions; C475418:ADIPOR1 protein, human; D054419:Receptors, Adiponectin; D005947:Glucose