GLP-1 Vésicules folliculaires extracellulaires : thérapie régénérative à cellules β dans le diabète sucréel de type 2 et les dysfonctionnements du PMOS

Auteurs-es

  • Shreya Pal University of Ottawa, Ottawa, ON, Canada
  • Sanya Anoop University of Ottawa, Ottawa, ON, Canada

DOI :

https://doi.org/10.18192/osurj.v5i2.7982

Résumé

Le diabète sucré de type 2 (DT2) se caractérise par un dysfonctionnement des cellules β et une perte de masse productrice d’insuline dans le pancréas (1). Les thérapies actuelles de réduction de la glycémie ralentissent la progression de la maladie mais ne parviennent pas à inverser le déclin des cellules β (2). Le syndrome ovarien métabolique polyendocrine (PMOS) et le DT2DM partagent des dysfonctionnements métaboliques sous-jacents, notamment la résistance à l’insuline et la signalisation inflammatoire chronique. Restaurer la santé des cellules β pourrait représenter une stratégie prometteuse pour améliorer la régulation métabolique, améliorer la gestion glycémique et potentiellement atténuer l’infertilité liée au PMOS (3).
Cette étude propose d’ingénier des vésicules extracellulaires dérivées du liquide folliculaire ovarien (FF-EV) pour soutenir la régénération pancréatique β-cellulaire. Les FF-EV visent à augmenter la masse cellulaire β, à améliorer la sécrétion d’insuline stimulée par le glucose et à réduire les dysfonctionnements reproductifs liés au DT2DM comme le PMOS (4).
Le liquide folliculaire de souris C57BL/6 stimulées hormonalement sera utilisé pour isoler les EV enrichies en microARN reproducteurs et en facteurs de croissance de type insuline (5). Ces appareils sont conçus pour afficher du peptide similaire-glucagon-1 (GLP-1) à leur surface membranaire par fusion avec la protéine membranaire lysosome-associée 2B (LAMP2B) ancrant les EV, permettant une captation sélective des cellules pancréatiques β via la liaison aux récepteurs GLP-1. Les VE conçus seront chargés de protéines cargo pro-régénératives (harmine et ARNm codant pour PDX1, NGN3 et MAFA), favorisant la prolifération des cellules β et la restauration de masse des cellules β (6).
Les formulations optimales de la cellule électrique seront testées chez des souris C57BL/6 (sans STZ, induite par STZ). La viabilité des β-cellules et les marqueurs diabétiques (Glut2, Glut4, INSR, IRS1/2) ont été évalués in vitro via la sécrétion d’insuline stimulée par le glucose, puis une évaluation in vivo de la prolifération des β pancréas (7). L’évaluation translationnelle utilisera des lignées β humaines et des organoïdes humains in vitro (follicules pancréas-ovaires) pour valider la récupération des cellules β et l’amélioration des paramètres métabolo-reproducteurs.

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Publié-e

2026-06-17

Numéro

Vol. 5 No. 2 (2026)

Rubrique

Research Proposals

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