Pharmacological inhibition of PI3Kδ opposes the progression of autoimmune diabetes in non-obese diabetic mice. (P5149)
Bibliographic record
Abstract
Abstract B-lymphocytes have been implicated in many autoimmune diseases, and non-obese diabetic (NOD) mice that lack B cells do not develop spontaneous autoimmune diabetes. The catalytic activity of PI3Kδ is important for B cell migration, activation, proliferation, and antigen presentation. We tested whether a PI3Kδ inhibitor could delay the onset or reduce the incidence of autoimmune diabetes in NOD mice. We found that preventative treatment of pre-diabetic NOD mice with GS-548202 (IC87114), a highly selective small molecule inhibitor of PI3Kδ, reduced the infiltration of inflammatory cells into the pancreatic islets and, accordingly, delayed and reduced the loss of glucose homeostasis. Diabetes developed in about 75% of vehicle-treated NOD mice by 18 weeks of age but in only 33% of GS-548202-treated animals at this same time point. Moreover in a therapeutic treatment mode, GS-548202 treatment conferred prolonged protection from progression to overt diabetes in a number of animals. Within 28 days, all of the NOD mice that received only the vehicle developed overt diabetes, with blood glucose levels rising substantially above 300 mg/dl. In contrast, 4 of the 7 GS-548202-treated NOD mice maintained their blood glucose levels below 300 mg/dl for at least 60 days after initiating treatment when they first exhibited blood glucose levels of 200-300mg/dl. These findings suggest that PI3Kδ inhibitors could be useful for managing autoimmune diabetes.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".