Cyanidin-3-O-Glucoside Treatment of Human Islets In Vitro Leads to an Augmentation of Autophagic Flux and a Decreased in Inflammatory Cell Markers
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".