This study examined the hypothesis that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) upregulates the insulin-independent signaling cascade of glucose metabolism. C2C12 myotubes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (0–50 nM). 1,25(OH)2D3 supplementation upregulated both insulin-independent (SIRT1) and insulin-dependent (p-IRS) signaling molecules, and stimulated the GLUT4 translocation, and glucose uptake in HG-treated myotubes. The effect of 1,25(OH)2D3 on IRS1 phosphorylation, GLUT4 translocation, and glucose uptake was attenuated in SIRT1-knockdown myotubes. Treatment with 1,25(OH)2D3, coupled with insulin, enhanced GLUT4 translocation and glucose uptake compared to treatment with either insulin or 1,25(OH)2D3 alone in HG-treated myotubes, which suggests that insulin-independent signaling molecules can contribute to the higher glucose metabolism observed in 1,25(OH)2D3 and insulin-treated cells. The data, therefore, suggest that 1,25(OH)2D3 increases glucose consumption by inducing SIRT1 activation, which in turn increases IRS1 phosphorylation and GLUT4 translocation in myotubes.
Vitamin D SIRT1 IRS1 GLUT4 Glucose metabolism
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The authors are supported by grants from the National Institutes of Health RO1 AT007442. This work was also supported by the Malcolm Feist Endowed Chair in Diabetes and by a fellowship from the Malcolm Feist Cardiovascular Research Endowment, LSU Health Sciences Center, Shreveport, Louisiana.
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Conflict of interest
The authors declare that they have no conflict of interest.
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