TITLE:
1,25-Dihydroxyvitamin D3 effects on the regulation of the insulin receptor gene in the hind limb muscle and heart of streptozotocin-induced diabetic rats
AUTHORS:
Consuelo Calle, Begoña Maestro, Moisés García-Arencibia
KEYWORDS:
1, 25-Dihydroxyvitamin D3; Streptozotocin-Induced Diabetic Rats; Hind Limb Muscle; Heart; Rat Insulin Receptor Gene; Computer Analysis; Vitamin D Response Element; Posttranscriptional Processes.
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.3 No.2,
April
30,
2013
ABSTRACT: In the present study, we examine the effects of the
treatment with 1,25-dihydroxyvitamin D3 [150 IU/Kg (3.75 μg/Kg) once
a day, for 15 days] to non-diabetic and streptozotocin-induced diabetic rats.
The results indicate that treatment with 1,25-dihydroxyvitamin D3 had minor effects in non-diabetic rats. The same treatment in
streptozotocin-induced diabetic rats, although it did not correct the
hyperglycemia and hypoinsulinemia induced by the diabetes, caused other actions
that could mean beneficial
effects on the amelioration of diabetes e.g., it
avoided body weight loss, increased calcium and phosphorus plasma levels, and corrected the
over-expression of the insulin receptor mRNA species of 9.5 and 7.5 Kb present
in the hind limb muscle and heart of these animals. These genomic 1,25-dihydroxyvitamin
D3 effects could involve
transcriptional mechanisms of repression mediated by vitamin D response elements in
the rat insulin receptor gene promoter. Using computer analysis of this promoter, we propose the -249/-235 bp VDRE (5’GGGTGACCCGGGGTT3’) with a pyrimidine (T) in the (+7)
position of the3’half-site as
the best candidate for negative control by 1,25-dihydroxy-vitamin D3.
In addition, posttranscriptional mechanisms of regulation could also be
implicated. Thus, computer inspection of the5’untranslated region of the rat insulin receptor
pre-mRNA indicated the presence of a virtual internal ribosome entry segment
whereas the computer inspection of the3’untranslated
region localized various destabilizing sequences,
including various AU-rich elements. We propose that through these virtual cis-regulatory sequences, 1,25-dihydroxyvitamin
D3 could control the
translation and stability of insulin receptor mRNA species in
the hind limb muscle and heart of diabetic rats.