GABA promotes β‐cell proliferation, but does not overcome impaired glucose homeostasis associated with diet‐induced obesity
Bibliographic record
Abstract
ABSTRACT γ‐Aminobutyric acid (GABA) administration has been shown to increase β‐cell mass, leading to a reversal of type 1 diabetes in mice. Whether GABA has any effect on β cells of healthy and prediabetic/glucose‐intolerant obese mice remains unknown. In the present study, we show that oral GABA administration ( ad libitum ) to mice indeed increased pancreatic β‐cell mass, which led to a modest enhancement in insulin secretion and glucose tolerance. However, GABA treatment did not further increase insulin‐positive islet area in high fat diet‐fed mice and was unable to prevent or reverse glucose intolerance and insulin resistance. Mechanistically, whether in vivo or in vitro , GABA treatment increased β‐cell proliferation. In vitro , the effect was shown to be mediated via the GABA A receptor. Single‐cell RNA sequencing analysis revealed that GABA preferentially up‐regulated pathways linked to β‐cell proliferation and simultaneously down‐regulated those networks required for other processes, including insulin biosynthesis and metabolism. Interestingly, single‐cell differential expression analysis revealed GABA treatment gave rise to a distinct subpopulation of β cells with a unique transcriptional signature, including urocortin 3 ( ucn3 ), wnt4 , and hepacam 2. Taken together, this study provides new mechanistic insight into the proliferative nature of GABA but suggests that β‐cell compensation associated with prediabetes overlaps with, and negates, its proliferative effects.—Untereiner, A., Abdo, S., Bhattacharjee, A., Gohil, H., Pourasgari, F., Ibeh, N., Lai, M., Batchuluun, B., Wong, A., Khuu, N., Liu, Y., Al Rijjal, D., Winegarden, N., Virtanen, C., Orser, B. A., Cabrera, O., Varga, G., Rocheleau, J., Dai, F. F., Wheeler, M. B. GABA promotes β‐cell proliferation, but does not overcome impaired glucose homeostasis associated with diet‐induced obesity. FASEB J. 33, 3968–3984 (2019). www.fasebj.org
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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 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".