Molecular and Cellular Biochemistry

, Volume 444, Issue 1–2, pp 103–108 | Cite as

1,25(OH)2-vitamin D3 upregulates glucose uptake mediated by SIRT1/IRS1/GLUT4 signaling cascade in C2C12 myotubes

  • Prasenjit Manna
  • Arunkumar E. Achari
  • Sushil K. Jain


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 



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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Prasenjit Manna
    • 1
  • Arunkumar E. Achari
    • 1
  • Sushil K. Jain
    • 1
  1. 1.Department of PediatricsLouisiana State University Health Sciences CenterShreveportUSA

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