R-spondin1 Deficiency Enhances β-Cell Neogenesis in a Murine Model of Diabetes
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Bibliographic record
Abstract
OBJECTIVE: The cWnt activator, R-spondin1 (Rspo1), regulates β-cell growth, function, and neogenesis, although its role in conditions such as streptozotocin (STZ)-induced diabetes is unknown. We hypothesized that Rspo1 deficiency enhances β-cell neogenesis in STZ-induced diabetes. METHODS: Wild-type (Rspo1) and knockout (Rspo1) mice were injected with STZ (40 mg/kg) for 5 days, followed by analysis of oral glucose and insulin tolerance, and were killed on day 6 (acute; 9-11 mice) or 32 (chronic; 11-16 mice). Immunohistochemistry was performed for β-cell apoptosis, proliferation, neogenesis, and markers of β-cell maturity. RESULTS: There was no difference in oral glucose handling between STZ-induced Rspo1 and Rspo1 mice, although Rspo1 mice demonstrated increased insulin sensitivity. β-cell mass, islet number, and islet size distribution did not differ between STZ-induced Rspo1 and Rspo1 mice, but Rspo1 animals had reduced β-cell apoptosis and increased numbers of insulin-positive ductal cells, indicating β-cell neogenesis. Furthermore, the increased β-cell regeneration observed in the Rspo1 animals was associated with a more differentiated/mature β-cell phenotype as assessed by increased immunopositivity for Nkx6.1, MafA, and GLUT2. CONCLUSIONS: These findings indicate that Rspo1 is a negative regulator of β-cell neogenesis, development, and survival in the face of STZ-induced diabetes, providing a therapeutic target for the enhancement of β-cell mass.
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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) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 it