TY - JOUR
T1 - 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
AU - Santoro, Massimo
AU - Masciullo, Marcella
AU - Bonvissuto, Davide
AU - Bianchi, Maria Laura Ester
AU - Michetti, Fabrizio
AU - Silvestri, Gabriella
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Insulin Receptor
KW - Myotonic dystrophy
KW - Insulin Receptor
KW - Myotonic dystrophy
UR - http://hdl.handle.net/10807/44107
U2 - 10.1007/s11010-013-1681-z
DO - 10.1007/s11010-013-1681-z
M3 - Article
SN - 0300-8177
VL - 380
SP - 259
EP - 265
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
ER -