Cyanidin-3-O-Glucoside Treatment of Human Islets In Vitro Leads to an Augmentation of Autophagic Flux and a Decreased in Inflammatory Cell Markers
Notice bibliographique
Résumé
Introduction Islet transplantation is currently being considered as an alternative treatment for Type I Diabetes. Despite recent progress, transplant patients continue to experience a progressive loss of insulin independence for reasons that are not well understood. Cyanidin-3-O-glucoside (C3G), an extract from Chinese bayberry, is an antioxidant that has been shown to be protective in vitro against the cell damage that may lead to transplant loss. In this study, we hypothesized that C3G is protective because of its ability to regulate autophagy; therefore, human islets treated with C3G should show an increased expression of autophagy marker LC3 and a decreased expression of inflammatory markers NLRP3 and IL-1β. Thus, we determined if autophagy is a possible mechanism by which C3G protects islets from damage in vitro. Materials and Methods Human islets (n=4-6) were obtained from the Alberta Diabetes Institute Human Islet Core laboratory and cultured in growth medium with or without C3G for 24 hours. Islets were then treated with human amylin, Aβ1-42, or rapamycin for 24 hours or H2O2 for 2 hours to mimic stresses encountered in the post-transplant environment. Samples of these islets were collected and stained for LC3, NLRP3, or IL-1β in addition to assessing their viability. Marker expression was visualized by immunofluorescence microscopy, and quantification of marker expression was performed using ImageJ software. Results and Discussion Islets treated only with human amylin or Aβ1-42 showed a significant decrease in cell viability compared to untreated islets (p < 0.05). Islets treated with human amylin or Aβ1-42 that received C3G presented a significant increase in cell viability compared to human amylin or Aβ1-42 without C3G (p < 0.05) indicating that C3G can protect human islets from the toxic effect of human amylin and Aβ1-42. When islets were treated with stress-inducing human amylin, Aβ1-42, rapamycin, or H2O2, LC3 expression was decreased, whereas expression of NLRP3 and IL-1β was increased. However, when islets were treated with C3G prior to the addition of a stress-inducing agent, LC3 expression was significantly increased (p ≤ 0.01) and NLRP3 and IL-1β expression was significantly decreased (p ≤ 0.01) compared to the samples not treated with C3G. These results suggest that C3G has beneficial effect on human islets by protecting them from damage induced by stresses encountered in the post-transplant environment. Conclusion Augmentation of autophagic flux is a likely mechanism by which C3G is protective against cellular stress in vitro. Further examination of the involvement of LC3 using siRNA is needed to determine the specific mechanism whereby C3G is protective. Alberta Diabetes Institute and University Hospital Foundation MF Grant (RES0027387).
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».