We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.
Here, we investigate the molecular differences between DM1 and DM2 using reverse transcriptase-polymerase chain reaction of troponin T (TnT) and the insulin receptor (IR), as well as immunoblotting of TnT in muscle biopsies from DM1 and DM2 patients.
Nevertheless the splicing pattern of the insulin receptor and MBNL1 transcripts, directly related to the DM2 phenotype, appears to be altered in in vitro differentiated DM2 myotubes.
The mutant RNA transcripts of DM1 and DM2 aberrantly affect the splicing of the same target RNAs, such as chloride channel 1 (ClC-1) and insulin receptor (INSR), resulting in their shared myotonia and insulin resistance.
Protein tyrosine phosphatase-1B (PTP-1B) dephosphorylates various receptor protein kinases in vitro, including the beta subunit of the insulin receptor, therefore representing a potential candidate to be involved in the polygenic pathogenesis of DM-2.