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

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Abstract

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.

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References

  1. Grant WB, Peiris AN (2010) Possible role of serum 25-hydroxyvitamin D in black-white health disparities in the United States. J Am Med Dir Assoc 11:617–628

    Article  PubMed  Google Scholar 

  2. Manna P, Achari AE, Jain SK (2017) Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Arch Biochem Biophys 615:22–34

    Article  PubMed  CAS  Google Scholar 

  3. Manna P, Jain SK (2012) Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization mediated by cystathionine-gamma-lyase (CSE) activation and H2S formation in 3T3L1 adipocytes. J Biol Chem 287:42324–42332

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Huang S, Czech MP (2007) The GLUT4 glucose transporter. Cell Metab 5:237–252

    Article  PubMed  CAS  Google Scholar 

  5. Stenbit AE, Tsao TS, Li J, Burcelin R, Geenen DL, Factor SM, Houseknecht K, Katz EB, Charron MJ (1997) GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 3:1096–1101

    Article  PubMed  CAS  Google Scholar 

  6. Wallberg-Henriksson H, Zierath JR (2001) GLUT4: a key player regulating glucose homeostasis? Insights from transgenic and knockout mice (review). Mol Membr Biol 18:205–211

    Article  PubMed  CAS  Google Scholar 

  7. Chang L, Chiang SH, Saltiel AR (2004) Insulin signaling and the regulation of glucose transport. Mol Med 10:65–71

    PubMed  PubMed Central  CAS  Google Scholar 

  8. Liang F, Kume S, Koya D (2009) SIRT1 and insulin resistance. Nat Rev Endocrinol 5:367–373

    Article  PubMed  CAS  Google Scholar 

  9. Patel N, Huang C, Klip A (2006) Cellular location of insulin-triggered signals and implications for glucose uptake. Pflugers Arch 451:499–510

    Article  PubMed  CAS  Google Scholar 

  10. Mastroyiannopoulos NP, Nicolaou P, Anayasa M, Uney JB, Phylactou LA (2012) Down-regulation of myogenin can reverse terminal muscle cell differentiation. PLoS ONE 7:e29896

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Candiloros H, Muller S, Zeghari N, Donner M, Drouin P, Ziegler O (1995) Decreased erythrocyte membrane fluidity in poorly controlled IDDM: influence of ketone bodies. Diabetes Care 18:549–551

    Article  PubMed  CAS  Google Scholar 

  12. Yaturu S, Davis J (2011) Prevalence of decreased vitamin D levels is high among veterans with diabetes and/or CKD. ISRN Endocrinol 2011:109458

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Manna P, Jain SK (2011) Hydrogen sulfide and L-cysteine increase phosphatidylinositol 3,4,5-trisphosphate (PIP3) and glucose utilization by inhibiting phosphatase and tensin homolog (PTEN) protein and activating phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/protein kinase Czeta/lambda (PKCzeta/lambda) in 3T3l1 adipocytes. J Biol Chem 286:39848–39859

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Vishwanath D, Srinivasan H, Patil MS, Seetarama S, Agrawal SK, Dixit MN, Dhar K (2013) Novel method to differentiate 3T3 L1 cells in vitro to produce highly sensitive adipocytes for a GLUT4 mediated glucose uptake using fluorescent glucose analog. J Cell Commun Signal 7:129–140

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jung DW, Ha HH, Zheng X, Chang YT, Williams DR (2011) Novel use of fluorescent glucose analogues to identify a new class of triazine-based insulin mimetics possessing useful secondary effects. Mol Biosyst 7:346–358

    Article  PubMed  CAS  Google Scholar 

  16. Mitri J, Muraru MD, Pittas AG (2011) Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr 65:1005–1015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, Murad MH, Kovacs CS (2012) The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev 33:456–492

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Kabadi SM, Lee BK, Liu L (2012) Joint effects of obesity and vitamin D insufficiency on insulin resistance and type 2 diabetes: results from the NHANES 2001–2006. Diabetes Care 35:2048–2054

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Schwalfenberg G (2008) Vitamin D and diabetes: improvement of glycemic control with vitamin D3 repletion. Can Fam Phys 54:864–866

    Google Scholar 

  20. Aljabri KS, Bokhari SA, Khan MJ (2010) Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency. Ann Saudi Med 30:454–458

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kayaniyil S, Vieth R, Retnakaran R, Knight JA, Qi Y, Gerstein HC, Perkins BA, Harris SB, Zinman B, Hanley AJ (2010) Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care 33:1379–1381

    Article  PubMed  PubMed Central  Google Scholar 

  22. Finkel T, Deng CX, Mostoslavsky R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460:587–591

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Haigis MC, Guarente LP (2006) Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction. Genes Dev 20:2913–2921

    Article  PubMed  CAS  Google Scholar 

  24. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305:390–392

    Article  PubMed  CAS  Google Scholar 

  25. Yoshizaki T, Milne JC, Imamura T, Schenk S, Sonoda N, Babendure JL, Lu JC, Smith JJ, Jirousek MR, Olefsky JM (2009) SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Mol Cell Biol 29:1363–1374

    Article  PubMed  CAS  Google Scholar 

  26. Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q (2007) SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab 6:307–319

    Article  PubMed  CAS  Google Scholar 

  27. Li J, Houseknecht KL, Stenbit AE, Katz EB, Charron MJ (2000) Reduced glucose uptake precedes insulin signaling defects in adipocytes from heterozygous GLUT4 knockout mice. FASEB J 14:1117–1125

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

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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  1. Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71103, USA

    Prasenjit Manna, Arunkumar E. Achari & Sushil K. Jain

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  1. Prasenjit Manna
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  2. Arunkumar E. Achari
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  3. Sushil K. Jain
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Correspondence to Sushil K. Jain.

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Manna, P., Achari, A.E. & Jain, S.K. 1,25(OH)2-vitamin D3 upregulates glucose uptake mediated by SIRT1/IRS1/GLUT4 signaling cascade in C2C12 myotubes. Mol Cell Biochem 444, 103–108 (2018). https://doi.org/10.1007/s11010-017-3235-2

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  • DOI: https://doi.org/10.1007/s11010-017-3235-2

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