Iterative Exposure of Clonal BRIN-BD11 Cells to Ninhydrin Enables Selection of Robust Toxin-Resistant Cells but With Decreased Gene Expression of Insulin Secretory Function
Bibliographic record
Abstract
OBJECTIVES: Prevention of pancreatic beta-cell destruction combined with preservation of insulin secretory function is an important goal for cell-based diabetes therapy. This study describes the generation and characteristics of toxin-resistant beta-cells. METHODS: By using iterative exposures to ninhydrin, a new class of robust ninhydrin-tolerant insulin-secreting BRIN-BD11 ninhydrin-tolerant (BRINnt) cells was generated. Low- and high-passage BRINnt cells were used to evaluate beta-cell function and tolerance against toxins in comparison with native BRIN-BD11 cells. Differences in viability, gene expression, insulin secretory function, antioxidant enzyme activity, DNA damage, and DNA repair efficiency were compared. RESULTS: BRIN-BD11 ninhydrin-tolerant cells exhibited resistance toward ninhydrin and hydrogen peroxide but not streptozotocin (STZ). Both total superoxide dismutase (SOD) and catalase enzyme activities of BRINnt cells were significantly enhanced, and ninhydrin-induced DNA damage was decreased. BRIN-BD11 ninhydrin-tolerant cells also exhibited enhanced DNA repair efficiency. However, this was accompanied by loss of secretagogue-induced insulin release, decreased cellular insulin content, and deficits in insulin and glucose transporter 2 gene expression. Prolonged culture of BRINnt cells in the absence of ninhydrin reversed the degenerated function of BRINnt cells but restored ninhydrin susceptibility. CONCLUSIONS: These data illustrate dissociation between beta-cell toxin resistance and secretory function, indicating difficulties in generation of robust and well-functioning cells using this approach.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".