Abstract
Backgroundthis study set out to examine the effects of the treatment with 1,25-dihydroxyvitamin D3 (1,25D3) [150 IU/Kg (3.75 μg/Kg) one a day, for 15 days] to non-diabetic rats and in rats rendered diabetic by a single injection of streptozotocin [65 mg/kg].Resultstreatment with 1,25D3 to non-diabetic rats did not affect the biochemical parameters measured in the plasma and urine of these animals. Likewise, insulin receptor expression in the kidney, liver, or adipose tissue and insulin-stimulated glucose transport in adipocytes from these animals were not affected either. Treatment with 1,25D3 to streptozotocin-induced diabetic rats did not correct the hyperglycemia, hypoinsulinemia, glycosuria or ketonemia induced by the diabetes, although it partially reversed the over-expression of the insulin receptor gene in the liver and adipose tissue, without altering the normal expression of this gene in the kidney. These effects were accompanied by a normalization of the number of insulin receptors without altering receptor affinity but improving the insulin response to glucose transport in adipocytes from these diabetic animals. Moreover, a computer search in the rat insulin receptor promoter revealed the existence of two candidate vitamin D response element (VDRE) sequences located at -256/-219 bp and -653/-620 bp, the first overlapped by three and the second by four AP-2-like sites.Conclusionthese genomic actions of 1,25D3 could represent beneficial effects associated with the amelioration of diabetes via mechanisms that possibly involve direct transcriptional activation of the rat insulin receptor gene. The candidate VDREs identified may respond to 1,25D3 via activation of the vitamin D receptor, although this remains to be investigated.
Highlights
It is known that vitamin D and especially its activated metabolite 1,25-dihydroxyvitamin D3 (1,25D3), are involved in controlling the normal function of the endocrine pancreas, and insulin secretion [1,2]
Vitamin D deficiency inhibits rat pancreatic secretion and turnover of insulin, leading to impaired glucose tolerance, while replacement therapy with 1,25D3, is able to reverse these abnormalities [3,4]. 1,25D3 affects the insulin receptor (IR), the protein to which insulin must bind to carry out its multiple biological actions in the cells
The results indicated that while treatment with 1,25D3 had practically no effect on non-diabetic rats, the same treatment in streptozotocin-induced diabetic rats corrected in part the over-expression of the IR gene in liver and adipose tissue, it did not revert the hyperglycemia, hypoinsulinemia, glycosuria or ketonemia of these diabetic animals
Summary
It is known that vitamin D and especially its activated metabolite 1,25-dihydroxyvitamin D3 (1,25D3), are involved in controlling the normal function of the endocrine pancreas, and insulin secretion [1,2]. 1,25D3 affects the insulin receptor (IR), the protein to which insulin must bind to carry out its multiple biological actions in the cells In this respect, our group has reported the first demonstration (page number not for citation purposes). Despite the different alterations in IR mRNA levels and insulin binding, streptozotocin-induced diabetic rats characteristically display insulin resistance [15,18,19]. In this diabetic model, the administration of 1,25D3 for 8 weeks was reported to improve diabetes attenuating pancreatic islet damage and decreasing the insulin requirements [12]
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