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Genomic actions of 1,25-dihydroxyvitamin D3 on insulin receptor gene expression, insulin receptor number and insulin activity in the kidney, liver and adipose tissue of streptozotocin-induced diabetic rats.

Calle C, Maestro B, García-Arencibia M - BMC Mol. Biol. (2008)

Bottom Line: 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. these 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University, 28040-Madrid, Spain. consuelo@med.ucm.es

ABSTRACT

Background: this study set out to examine the effects of the treatment with 1,25-dihydroxyvitamin D3 (1,25D3) [150 IU/Kg (3.75 microg/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].

Results: treatment 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.

Conclusion: these 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.

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Insulin receptor number per cell. Insulin receptor number in epididymal adipocytes from sham-treated rats (Control), rats treated with 1,25D3 [150 IU/Kg (3.75 μg/Kg) one a day, for 15 days] (1,25D3), streptozotocin-induced diabetic rats (STZ) and streptozotocin-induced diabetic rats treated with 1,25D3 (STZ+1,25D3). Values are the mean ± SEM of 3–9 determinations in each group. a p < 0.05 vs. Control-rats; b p < 0.05 vs. 1,25D3-rats; and c p < 0.05 vs. STZ-rats.
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Figure 2: Insulin receptor number per cell. Insulin receptor number in epididymal adipocytes from sham-treated rats (Control), rats treated with 1,25D3 [150 IU/Kg (3.75 μg/Kg) one a day, for 15 days] (1,25D3), streptozotocin-induced diabetic rats (STZ) and streptozotocin-induced diabetic rats treated with 1,25D3 (STZ+1,25D3). Values are the mean ± SEM of 3–9 determinations in each group. a p < 0.05 vs. Control-rats; b p < 0.05 vs. 1,25D3-rats; and c p < 0.05 vs. STZ-rats.

Mentions: Insulin binding studies showed that treatment with 1,25D3 to non-diabetic rats did not alter IR number or IR affinity as reflected by the ED:50 value in adipocytes of these animals (Figure 2 and Table 3). Streptozotocin injection produced a 64% decrease in the number of IRs without altering IR affinity. Treatment with 1,25D3 to streptozotocin-induced diabetic rats inverted the decrease in the IR number induced by the diabetes to values not significantly different from those observed in control adipocytes and without altering IR affinity (Figure 2 and Table 3).


Genomic actions of 1,25-dihydroxyvitamin D3 on insulin receptor gene expression, insulin receptor number and insulin activity in the kidney, liver and adipose tissue of streptozotocin-induced diabetic rats.

Calle C, Maestro B, García-Arencibia M - BMC Mol. Biol. (2008)

Insulin receptor number per cell. Insulin receptor number in epididymal adipocytes from sham-treated rats (Control), rats treated with 1,25D3 [150 IU/Kg (3.75 μg/Kg) one a day, for 15 days] (1,25D3), streptozotocin-induced diabetic rats (STZ) and streptozotocin-induced diabetic rats treated with 1,25D3 (STZ+1,25D3). Values are the mean ± SEM of 3–9 determinations in each group. a p < 0.05 vs. Control-rats; b p < 0.05 vs. 1,25D3-rats; and c p < 0.05 vs. STZ-rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2533347&req=5

Figure 2: Insulin receptor number per cell. Insulin receptor number in epididymal adipocytes from sham-treated rats (Control), rats treated with 1,25D3 [150 IU/Kg (3.75 μg/Kg) one a day, for 15 days] (1,25D3), streptozotocin-induced diabetic rats (STZ) and streptozotocin-induced diabetic rats treated with 1,25D3 (STZ+1,25D3). Values are the mean ± SEM of 3–9 determinations in each group. a p < 0.05 vs. Control-rats; b p < 0.05 vs. 1,25D3-rats; and c p < 0.05 vs. STZ-rats.
Mentions: Insulin binding studies showed that treatment with 1,25D3 to non-diabetic rats did not alter IR number or IR affinity as reflected by the ED:50 value in adipocytes of these animals (Figure 2 and Table 3). Streptozotocin injection produced a 64% decrease in the number of IRs without altering IR affinity. Treatment with 1,25D3 to streptozotocin-induced diabetic rats inverted the decrease in the IR number induced by the diabetes to values not significantly different from those observed in control adipocytes and without altering IR affinity (Figure 2 and Table 3).

Bottom Line: 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. these 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University, 28040-Madrid, Spain. consuelo@med.ucm.es

ABSTRACT

Background: this study set out to examine the effects of the treatment with 1,25-dihydroxyvitamin D3 (1,25D3) [150 IU/Kg (3.75 microg/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].

Results: treatment 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.

Conclusion: these 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.

Show MeSH
Related in: MedlinePlus