PhD Scientific Days 2024

Pharmaceutical Sciences and Health Technologies I.

Resveratrol Restores Insulin Signaling in in vitro Streptozotocin Induced Neurodegenerative Model

Előadó neve

Dr. Varga, Kamilla

Neptun code

FC2S6I

Előadó munkahelye

Department of Pharmacology, Semmelweis University

Előadó telefonszáma

+36703258604

Előadó e-mail címe

varga.kamilla@phd.semmelweis.hu

Az előadás címe

Resveratrol Restores Insulin Signaling in in vitro Streptozotocin Induced Neurodegenerative Model

Szerző(k) neve és munkahelye

Kamilla Varga¹, Anna-Lena Friesenhahn², Florian Emanuel Zymela², Virag Kovacs³, Csenge Boroczky³, Noemi Sikur³, Alexandra Paszternak³, Tamas Tabi³, Stefan Wolfl²

1: Semmelweis Egyetem GyTK Gyógyszerhatástani Intézet
2: Institute for Pharmacy und Molecular Biotechnology, Ruprecht Karls University, Heidelberg
3: Department of Pharmacodynamics, Semmelweis University, Budapest

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences and Health Technologies I.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Resveratrol, a natural phytoalexin, has been shown beneficial in age related disorders like Alzheimer’s disease. It has been proven to delay the loss of memory function and be considered as a neuroprotective agent. However, the underlying mechanisms are still unknown and the research on the effect of resveratrol on central insulin resistance is lacking. Addressing insulin sensitivity could hold significant therapeutic value in treating neurodegenerative conditions.
Aim: Examining the effect of resveratrol on insulin signaling and mitochondria in our previously described in vitro neurodegeneration model.
Methods: Insulin resistance has been induced by 1mM streptozotocin in retinoic acid differentiated neuron-like SH-SY5Y cells. Cell viability was assessed with SRB reagent. The phosphorylation of IRS1, Akt, GSK3β and mTOR were investigated by Western blot and ELISA-based microarray technique. The effect of resveratrol on mitochondrial biogenesis was assessed by Mitotracker staining and measuring TFAM and ATP5B mRNA expression.
Results: Resveratrol concentration-dependently improved insulin induced proliferation in streptozotocin treated cells. It also reduced the Ser(312) phosphorylation of IRS1 commonly associated with insulin resistance and decreased the IC50 value of Tyr(895) phosphorylation needed for activation. We observed similar insulin sensitizing effect on the components of downstream pathway; mTOR, p70S6K, Akt and GSK3β. Streptozotocin decreased the expression of mitochondrial transcriptional factor TFAM, complex V subunit ATP5B and energy sensing AMPK, and resveratrol could reverse these alterations and further increased their expression without altering the number of mitochondria.
Conclusion: Our results revealed that resveratrol can improve insulin signaling in streptozotocin induced insulin resistance even at its initial step of IRS1 phosphorylation. Its sensitizing effect include not only the metabolic effect, but the proliferative effect as well. The pathway may involve mitochondrial biogenesis and improving quality control.
Funding: Our project was funded by Semmelweis 250+ Excellence PhD Scholarship (EFOP-3.6.3-VEKOP-16-2017-00009) and Jellinek Harry Scholarship „Improvement of scientific workshops for medical, health science and pharmacy education” (EFOP-3.6.3.-VEKOP-16-2017-00009) with Ruprecht Karls University.

University

Semmelweis University

Supervisor

Tamas Tabi

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6064

Start

17:45

End

17:55