Skip to main content
SpringerLink
Log in

Insulin induces Ca2+ oscillations in white fat adipocytes via PI3K and PLC

  • Articles
  • Published:
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Adipocytes of white adipose tissue are the cells maintaining glucose homeostasis in an organism, which is controlled by insulin. Insulin stimulates the translocation of glucose transporter GLUT4 from the cytosol into the cell membrane, as well as glucose transport and utilization in these cells. Here we show that insulin-induced [Ca2+]i oscillations are supported by the two signaling pathways involving: (1) phosphoinositide 3-kinase (PI3K), protein kinase B (Akt/PKB), endothelial NO synthase (eNOS), nitric oxide (NO), and ryanodine receptor (RyR) and (2) phospholipase C (PLC) and inositol 3-phosphate receptor (IP3R). Thus, the PI3K Akt/PKB signaling pathway initiates not only metabolic but also Ca2+-signaling pathways in response to insulin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. White M.F. 1997. The insulin signalling system and the IRS proteins. Diabetologia. 40, 2–17.

    Article  Google Scholar 

  2. Sun X.J., Rothenberg P., Kahn CR., Backer J.M., Araki E., Wilden P.A., Cahill D.A., Goldstein B.J., White M.F. 1991. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature. 352, 73–77.

    Article  CAS  PubMed  Google Scholar 

  3. Giorgetti S., Ballotti R., Kowalski-Chauvel A., Cormont M., van Obberghen E. 1992. Insulin stimulates phosphatidylinositol-3-kinase activity in rat adipocytes. Eur. J. Biochem. 207 (2), 599–606.

    Article  CAS  PubMed  Google Scholar 

  4. Vanhaesebroeck B., Alessi D.R. 2000. The PI3KPDK1 connection: More than just a road to PKB. J. Biochem. 346, 561–576.

    CAS  Google Scholar 

  5. Cohen P., Alessi D.R., Cross D.A. 1997. PDK1, one of the missing links in insulin signal transduction? FEBS Lett. 410, 3–10.

    Article  CAS  PubMed  Google Scholar 

  6. Hajduch E., Litherland G.J., Hundal HS. 2001. Protein kinase B (PKB/Akt)–a key regulator of glucose transport? FEBS Lett. 492, 199–203.

    Article  CAS  PubMed  Google Scholar 

  7. Dolgacheva L.P., Turovsky E.A., Turovskaya M.V., Zinchenko V.P., Dynnik V.V. 2012. a-Adrenergic control of two Ca2+-signaling pathways of adipocytes. Ross. Fiziol. Zh. im. I.M. Sechenova (Rus.). 98 (12), 47–54.

    Google Scholar 

  8. Turovsky E.A., Turovskaya M.V., Dolgacheva L.P., Zinchenko V.P., Dynnik V.V. 2013. Acetylcholine promotes Ca2+ and NO-oscillations in adipocytes implicating Ca2+ NO cGMP cADP-ribose Ca2+ positive feedback loop–modulatory effects of norepinephrine and atrial natriuretic peptide. PLoS One. 8 (5), 1–18.

    Article  Google Scholar 

  9. Turovsky E.A., Turovskaya M.V., Tolmacheva A.V., Dolgacheva L.P., Zinchenko V.P., Dynnik V.V. 2013. Resistance of mouse adipocytes to noradrenalin in obesity and type 2 diabetes mellitus. Fundamental’nye issledovaniya (Rus.). 1 (3), 595–599.

    Google Scholar 

  10. Trevellin E., Scorzeto M., Olivieri M., Granzotto M., Valerio A., Tedesco L., Fabris R., Serra R., Quarta M., Reggiani C., Nisoli E., Vettor R. 2014. Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes. 63 (8), 2800–2811.

    Article  CAS  PubMed  Google Scholar 

  11. Nagano T., Yoshimura T. 2002. Bioimaging of nitric oxide. Chem. Rev. 102 (4), 1235–1270.

    Article  CAS  PubMed  Google Scholar 

  12. Fulton D., Gratton J.P., McCabe T.J., Fontana J., Fujio Y., Walsh K., Franke T.F., Papapetropoulos A., Sessa W.C. 1999. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 399 (6736), 597–601.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Dimmeler S., Fleming I., Fisslthaler B., Hermann C., Busse R., Zeiher A.M. 1999. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 399 (6736), 601–605.

    Article  CAS  PubMed  Google Scholar 

  14. Prakash Y.S., Kannan M.S., Walseth T.F., Sieck G.C. 1998. Role of cyclic ADP-ribose in the regulation of [Ca2+]i in porcine tracheal smooth muscle. Am. J. Physiol. 274 (6), 1653–1660.

    Google Scholar 

  15. Jung U.J., Choi M.S. 2014. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int. J. Mol. Sci. 15 (4), 6184–223.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Lillioja S., Mott D.M., Spraul M., Ferraro R., Foley J.E., Ravussin E., Knowler W.C., Bennett P.H., Bogardus C. 1993. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. N. Engl. J. Med. 329, 1988–1992.

    Article  CAS  PubMed  Google Scholar 

  17. Cheatham B., Vlahos C., Cheatham L., Wang L., Blenis J., Kahn C. 1994. Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. 14, 4902–4911.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Okada T., Kawano Y., Sakakibara T., Hazeki O., Ui M. 1994. Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. J. Biol. Chem. 269, 3568–3573.

    CAS  PubMed  Google Scholar 

  19. Alessi D.R., Downes C.P. 1998. The role of PI 3-kinase in insulin action. Biochim. Biophys. Acta. 1436, 151–164.

    Article  CAS  PubMed  Google Scholar 

  20. Whiteman E.L., Cho H., Birnbaum M.J. 2002. Role of Akt/protein kinase B in metabolism. Trends Endocrinol. Metab. 13, 444–451.

    Article  CAS  PubMed  Google Scholar 

  21. Gonzalez E., McGraw T.E. 2009. The Akt kinases: Isoform specificity in metabolism and cancer. Cell Cycle. 8 (16), 2502–2508.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Hanada M., Feng J., Hemmings B.A. 2004. Structure, regulation and function of PKB/Akt–a major therapeutic target. Biochim. Biophys. Acta. 1697, 3–16.

    Article  CAS  PubMed  Google Scholar 

  23. Manning B.D., Cantley L.C. 2007. Akt/PKB signaling: Navigating downstream. Cell. 129, 1261–1274.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Pfeffer S., Aivazian D. 2004. Targeting Rab GTPases to distinct membrane compartments. Nat. Rev. Mol. Cell. Biol. 5, 886–896.

    Article  CAS  PubMed  Google Scholar 

  25. Stenmark H. 2009. Rab GTPases as coordinators of vesicle traffic. Nat. Rev. Mol. Cell. Biol. 10, 513–525.

    Article  CAS  PubMed  Google Scholar 

  26. Zerial M., McBride H. 2001. Rab proteins as membrane organizers. Nat. Rev. Mol. Cell. Biol. 2, 107–117.

    Article  CAS  PubMed  Google Scholar 

  27. Kane S., Sano H., Liu S.C., Asara J.M., Lane W.S., Garner C.C., Lienhard G.E. 2002. A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain. J. Biol. Chem. 277, 22115–22118.

    CAS  PubMed  Google Scholar 

  28. Tan S.X., Ng Y., Burchfield J.G., Ramm G., Lambright D.G., Stockli J., James D.E. 2012. The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes. Mol. Cell. Biol. 32 (24), 4946–4959.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Yu H., Rathore S.S., Davis E.M., Ouyang Y., Shen J. 2013. Doc2b promotes GLUT4 exocytosis by activating the SNARE-mediated fusion reaction in a calciumand membrane bending-dependent manner. Mol. Biol. Cell. 24 (8), 1176–1184.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Roy D., Perreault M., Marette A. 1998. Insulin stimulation of glucose uptake in skeletal muscles and adipose tissues in vivo is NO dependent. Am. J. Physiol. 274 (4 Pt 1), 692–699.

    Google Scholar 

  31. Hong Y.H., Betik A.C., McConell G.K. 2014. Role of nitric oxide in skeletal muscle glucose uptake during exercise. Exp. Physiol. 99 (12), 1569–1573.

    Article  CAS  PubMed  Google Scholar 

  32. Masters B.S.S., McMillan K., Sheta E.A., Nishimura J.S., Roman L.J., Martasek P. 1996. Neuronal nitric oxide synthase, a modular enzyme formed by convergent evolution: Structure studies of a cysteine thiolate-liganded heme protein that hydroxylates L-arginine to produce NO as a cellular signal. FASEB J. 10, 552–558.

    CAS  PubMed  Google Scholar 

  33. Fleming I. 2010. Molecular mechanisms underlying the activation of eNOS. Pflügers Archiv. 459, 793–806.

    Article  CAS  PubMed  Google Scholar 

  34. Forstermann U., Sessa W.C. 2012. Nitric oxide synthases: Regulation and function. Eur. Heart J. 33, 829–837.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Venema R.C., Sayegh H.S., Kent J.D., Harrison D.G. 1996. Identification, characterization, and comparison of the calmodulin-binding domains of the endothelial and inducible nitric oxide synthases. J. Biol. Chem. 271, 6435–6440.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, ul. Institutskaya 3, Pushchino, Moscow oblast, 142290, Russia

    E. A. Turovsky, M. V. Turovskaya, V. P. Zinchenko, V. V. Dynnik & L. P. Dolgacheva

  2. Pushchino State Institute of Natural Sciences, ul. Institutskaya 3, Pushchino, Moscow oblast, 142290, Russia

    V. P. Zinchenko & L. P. Dolgacheva

  3. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, ul. Institutskaya 3, Pushchino, Moscow oblast, 142290, Russia

    V. V. Dynnik

Authors
  1. E. A. Turovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Turovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. P. Zinchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. V. Dynnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. P. Dolgacheva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. P. Dolgacheva.

Additional information

Original Russian Text © E.A. Turovsky, M.V. Turovskaya, V.P. Zinchenko, V.V. Dynnik, L.P. Dolgacheva, 2015, published in Biologicheskie Membrany, 2015, Vol. 32, No. 5–6, pp. 429–436.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Turovsky, E.A., Turovskaya, M.V., Zinchenko, V.P. et al. Insulin induces Ca2+ oscillations in white fat adipocytes via PI3K and PLC. Biochem. Moscow Suppl. Ser. A 10, 53–59 (2016). https://doi.org/10.1134/S1990747815050189

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990747815050189

Keywords

Search

Navigation