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The PI3K/Akt Cascade Is Involved in the Antidiabetic Effect of Compound GSB-214, a Low-Molecular-Weight BDNF Mimetic

  • PHARMACOLOGY AND TOXICOLOGY
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Bulletin of Experimental Biology and Medicine Aims and scope

In our previous studies on the streptozotocin model of diabetes we hypothesized that activation of the PI3K/Akt signaling pathway is essential for the realization of the antidiabetic effect of low-molecular-weight NGF and BDNF mimetics. Here we analyze the effect of a specific PI3K/Akt pathway inhibitor (LY 294002) on the antidiabetic effect of the BDNF loop 1 mimetic GSB-214. The experiments on C57BL/6 mice with streptozotocin-induced diabetes showed that GSB-214 attenuated the hyperglycemic effect of streptozotocin and prevented weight loss typical of diabetes, while LY 294002 eliminated these effects of GSB-214. These findings clearly demonstrate the involvement of PI3K/Akt pathway in the implementation of the effects of this low-molecular-weight BDNF mimetic.

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References

  1. Gudasheva TA, Logvinov IO, Povarnina PY, Antipova TA, Seredenin SB. Analysis of dependence of antidepressant properties of Trkb receptor ligands on MAP-kinase pathway activation. Dokl. Biochem. Biophysics. 2015;460(1):20-22.

    CAS  Google Scholar 

  2. Gudasheva TA, Tarasyuk AV, Pomogaibo SV, Logvinov IO, Povarnina PYu, Antipova TA, Seredenin SB. Design and synthesis of dipeptide mimetics of the brain-derived neurotrophic factor. Russ. J. Bioorgan. Chem. 2012;38(3):243-252.

    CAS  Google Scholar 

  3. Ostrovskaya RU, Yagubova SS, Gudasheva TA, Seredenin SB. Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type of Activation of Post-Receptor Signaling Pathways. Bull. Exp. Biol. Med. 2018;164(6):734- 737. https://doi.org/10.1007/s10517-018-4069-y

    Article  CAS  PubMed  Google Scholar 

  4. Seredenin SB, Gudasheva TA. Patent Ru No. 2410392. Dipeptide mimetics of NGF and BDNF neurotrophins. Bull. No. 24. Published August 27, 2010.

  5. Bathina S, Srinivas N, Das UN. BDNF protects pancreatic β cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro. Metabolism. 2016;65(5):667-684. https://doi.org/10.1016/j.metabol.2016.01.016

    Article  CAS  PubMed  Google Scholar 

  6. Bernal-Mizrachi E, Fatrai S, Johnson JD, Ohsugi M, Otani K, Han Z, Polonsky KS, Permutt MA. Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells. J. Clin. Invest. 2004;114(7):928-936.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA. Islet beta cell expression of constitutively active Akt1/ PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J. Clin. Invest. 2001;108(11):1631-1638.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Cui W, Zhang Y, Lu D, Ren M, Yuan G. Upregulation of p-Akt by glial cell line-derived neurotrophic factor ameliorates cell apoptosis in the hippocampus of rats with streptozotocin-induced diabetic encephalopathy. Mol. Med. Rep. 2016;13(1):543-549. https://doi.org/10.3892/mmr.2015.4507

    Article  CAS  PubMed  Google Scholar 

  9. Elghazi L, Rachdi L, Weiss A.J, Cras-Méneur C, Bernal-Mizrachi E. Regulation of beta-cell mass and function by the Akt/ protein kinase B signalling pathway. Diabetes Obes. Metab. 2007;9(Suppl 2):147-157.

    CAS  PubMed  Google Scholar 

  10. Garofalo RS, Orena SJ, Rafidi K, Torchia AJ, Stock JL, Hildebrandt AL, Coskran T, Black SC, Brees DJ, Wicks JR, Mc- Neish JD, Coleman KG. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Invest. 2003;112(2):197-208

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Gudasheva TA, Povarnina P, Logvinov IO, Antipova TA, Seredenin SB. Mimetics of brain-derived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats. Drug Des. Devel. Ther. 2016;10:3545-3553.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Nakagawa T, Ogawa Y, Ebihara K, Yamanaka M, Tsuchida A, Taiji M, Noguchi H, Nakao K. Anti-obesity and anti-diabetic effects of brain-derived neurotrophic factor in rodent models of leptin resistance. Int. J. Obes. Relat. Metab. Disord. 2003;27(5):557-565.

    CAS  PubMed  Google Scholar 

  13. Noble EE, Billington CJ, Kotz CM, Wang C. The lighter side of BDNF. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011;300(5):R1053-R1069. https://doi.org/10.1152/ajpregu.00776.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yousif MH. Phosphoinositide 3-kinase contributes to diabetesinduced abnormal vascular reactivity in rat perfused mesenteric bed. Cell Biochem. Funct. 2008;26(4):451-458. https://doi.org/10.1002/cbf.1463

    Article  CAS  PubMed  Google Scholar 

  15. Zdychová J, Komers R. Emerging role of Akt kinase/protein kinase B signaling in pathophysiology of diabetes and its complications. Physiol. Res. 2005;54(1):1-16.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia

    S. S. Yagubova, R. U. Ostrovskaya, T. A. Gudasheva & S. B. Seredenin

Authors
  1. S. S. Yagubova
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  2. R. U. Ostrovskaya
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  3. T. A. Gudasheva
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  4. S. B. Seredenin
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Corresponding author

Correspondence to R. U. Ostrovskaya.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 6, pp. 712-715, June, 2020

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Yagubova, S.S., Ostrovskaya, R.U., Gudasheva, T.A. et al. The PI3K/Akt Cascade Is Involved in the Antidiabetic Effect of Compound GSB-214, a Low-Molecular-Weight BDNF Mimetic. Bull Exp Biol Med 169, 771–774 (2020). https://doi.org/10.1007/s10517-020-04975-7

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  • DOI: https://doi.org/10.1007/s10517-020-04975-7

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