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

Abstract

<p> <span style="font-size:10.0pt;"><span style="font-family:Verdana;">In the present study, we examine the effects of the treatment with 1,25-dihydroxyvitamin D</span>_{<span style="font-family:Verdana;">3</span>}<span style="font-family:Verdana;"> [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 D</span>_{<span style="font-family:Verdana;">3</span>}<span style="font-family:Verdana;"> 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 </span></span><span style="font-size:10pt;font-family:Verdana;">could mean beneficial effects on the amelioration of diabetes</span><span style="font-size:10pt;font-family:Verdana;"> e.g., it avoided body weight loss, increased calcium and phosphorus plasma levels, and </span><span style="font-size:10.0pt;"><span style="font-family:Verdana;">corrected</span><i></i><span style="font-family:Verdana;">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 </span></span><span style="font-size:10.0pt;"><span style="font-family:Verdana;">1,25-dihydroxyvitamin D</span>_{<span style="font-family:Verdana;">3</span>}<span style="font-family:Verdana;"> effects </span></span><span style="font-size:10pt;font-family:Verdana;">could involve transcriptional mechanisms of repression mediated by</span><span style="font-size:10pt;font-family:Verdana;"> vitamin D response elements </span><span style="font-size:10pt;font-family:Verdana;">in the rat insulin receptor gene promoter</span><span style="font-size:10pt;font-family:Verdana;">. Using</span><span style="font-size:10pt;font-family:Verdana;"> computer analysis of this promoter, we propose the -</span><span style="font-size:10pt;font-family:Verdana;">249/-</span><span style="font-size:10.0pt;"><span style="font-family:Verdana;">235 bp VDRE (5’</span><u><span style="font-family:Verdana;">GGGTGA</span></u><span style="font-family:Verdana;">CCC</span><u><span style="font-family:Verdana;">GGGGTT</span></u><span style="font-family:Verdana;">3’) with a pyrimidine (T) in the (+7) position of the3’half-site as the </span><span style="font-family:Verdana;">best candidate for negative control by </span></span><span style="font-size:10pt;font-family:Verdana;">1,25-dihydroxy-</span><span style="font-size:10.0pt;"><span style="font-family:Verdana;">vitamin D</span>_{<span style="font-family:Verdana;">3</span>}<span style="font-family:Verdana;">. In addition, posttranscriptional mecha</span></span><span style="font-size:10pt;font-family:Verdana;">nisms 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 segme...