Alternative splicing of human insulin receptor gene (INSR) in type i and type II skeletal muscle fibers of patients with myotonic dystrophy type 1 and type 2

Massimo Santoro, Marcella Masciullo, Davide Bonvissuto, Maria Laura Ester Bianchi, Fabrizio Michetti, Gabriella Silvestri

Research output: Contribution to journalArticlepeer-review

Abstract

INSR, one of those genes aberrantly expressed in myotonic dystrophy type 1 (DM1) and type 2 (DM2) due to a toxic RNA effect, encodes for the insulin receptor (IR). Its expression is regulated by alternative splicing generating two isoforms: IR-A, which predominates in embryonic tissue, and IR-B, which is highly expressed in adult, insulin-responsive tissues (skeletal muscle, liver, and adipose tissue). The aberrant INSR expression detected in DM1 and DM2 muscles tissues, characterized by a relative increase of IR-A versus IR-B, was pathogenically related to the insulin resistance occurring in DM patients. To assess if differences in the aberrant splicing of INSR could underlie the distinct fiber type involvement observed in DM1 and DM2 muscle tissues, we have used laser capture microdissection (LCM) and RT-PCR, comparing the alternative splicing of INSR in type I and type II muscle fibers isolated from muscle biopsies of DM1, DM2 patients and controls. In the controls, the relative amounts of IR-A and IR-B showed no obvious differences between type I and type II fibers, as in the whole muscle tissue. In DM1 and DM2 patients, both fiber types showed a similar, relative increase of IR-A versus IR-B, as also evident in the whole muscle tissue. Our data suggest that the distinct fiber type involvement in DM1 and DM2 muscle tissues would not be related to qualitative differences in the expression of INSR. LCM can represent a powerful tool to give a better understanding of the pathogenesis of myotonic dystrophies, as well as other myopathies.

Original languageEnglish
Pages (from-to)259-265
Number of pages7
JournalMolecular and Cellular Biochemistry
Volume380
Issue number1-2
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Insulin receptor
  • Laser capture micro dissection (LCM)
  • Myotonic dystrophy
  • Type I muscle fiber
  • Type II muscle fiber

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

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