PhD Scientific Days 2023

Pharmaceutical Sciences I.

Role of resveratrol in in vitro neuronal insulin signaling

Előadó neve

Varga, Kamilla

Neptun code

FC2S6I

Előadó munkahelye

Department of Pharmacodynamics, Semmelweis University

Előadó telefonszáma

+36 1 459 1500/56219

Előadó e-mail címe

varga.kamilla@phd.semmelweis.hu

Az előadás címe

Role of resveratrol in in vitro neuronal insulin signaling

Szerző(k) neve és munkahelye

Kamilla Varga: Department of Pharmacodynamics, Semmelweis University, Budapest
Anna-Lena Friesenhahn: Institut für Pharmazie und Molekulare Biotechnologie, Ruprecht Karls University, Heidelberg
Florian Emanuel Zymela: Institut für Pharmazie und Molekulare Biotechnologie, Ruprecht Karls University, Heidelberg
Virág Kovács: Department of Pharmacodynamics, Semmelweis University, Budapest
Eszter Torma: Department of Pharmacodynamics, Semmelweis University, Budapest
Dimitrisz Patakfalvi: Department of Pharmacodynamics, Semmelweis University, Budapest
Csenge Boroczky: Department of Pharmacodynamics, Semmelweis University, Budapest
Noémi Sikur: Department of Pharmacodynamics, Semmelweis University, Budapest
Alexandra Barcza-Paszternák: Department of Pharmacodynamics, Semmelweis University, Budapest
Tamás Tábi: Department of Pharmacodynamics, Semmelweis University, Budapest
Stefan Wölfl: Institut für Pharmazie und Molekulare Biotechnologie, Ruprecht Karls University, Heidelberg

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences I.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction: Brain insulin resistance has been associated with cognitive decline in several neurodegenerative diseases like Alzheimer’s disease, and improving insulin sensitivity could be a valuable target in its treatment. Resveratrol, a natural antioxidant compound has been shown to delay the loss of memory function in numerous age-related neurodegenerative diseases therefore considered as a neuroprotective agent. The underlying mechanisms, however are still unknown and the research on the effect of resveratrol on central insulin resistance is lacking.
Aim: Investigating the effect of resveratrol on central insulin signaling in our previously described in vitro neurodegeneration model.
Methods: Insulin resistance has been induced by 1mM streptozotocin in retinoic acid differentiated SH-SY5Y cells. Cell viability was measured with SRB reagent and Hoest/PI staining. The phosphorylation of IRS1, Akt, GSK3β, mTOR, and p70S6K were investigated with Western blot and ELISA-based microarray technique. The effect of resveratrol on mitochondrial biogenesis was assessed by measuring TFAM and ATP5B mRNA expression.
Results: Resveratrol concentration-dependently improved insulin induced proliferation in streptozotocin treated cells. It also decreased the Ser(312) phosphorylation of IRS1 commonly associated with insulin resistance and increased 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 transcription of mitochondrial transcriptional factor TFAM, and complex V subunit ATP5B and energy sensing AMPK, but resveratrol could reverse and further increase their expression.
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 includes 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 and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Tamás Tábi docent of Department of Pharmacodynamics

Publication of my abstract

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

Előadó pecsétszáma/működési nyilvántartási száma

17002

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6064

Start

11:00

End

11:15

Authors (legacy)

Kamilla Varga: Department of Pharmacodynamics, Semmelweis University, Budapest
Anna-Lena Friesenhahn: Institut für Pharmazie und Molekulare Biotechnologie, Ruprecht Karls University, Heidelberg
Florian Emanuel Zymela: Institut für Pharmazie und Molekulare Biotechnologie, Ruprecht Karls University, Heidelberg
Virág Kovács: Department of Pharmacodynamics, Semmelweis University, Budapest
Eszter Torma: Department of Pharmacodynamics, Semmelweis University, Budapest
Dimitrisz Patakfalvi: Department of Pharmacodynamics, Semmelweis University, Budapest
Csenge Boroczky: Department of Pharmacodynamics, Semmelweis University, Budapest
Noémi Sikur: Department of Pharmacodynamics, Semmelweis University, Budapest
Alexandra Barcza-Paszternák: Department of Pharmacodynamics, Semmelweis University, Budapest
Tamás Tábi: Department of Pharmacodynamics, Semmelweis University, Budapest
Stefan Wölfl: Institut für Pharmazie und Molekulare Biotechnologie, Ruprecht Karls University, Heidelberg