AMPK β1 activation suppresses antipsychotic‐induced hyperglycemia in mice
Bibliographic record
Abstract
Olanzapine (OLZ) is a second‐generation antipsychotic that is used to treat schizophrenia but also causes acute hyperglycemia. This study aimed to determine if the ablation of AMPK β1‐containing complexes potentiates acute OLZ‐induced metabolic dysfunction and if the activation of AMPK β1 suppresses these effects. Female AMPK β1 ‐/‐ or wild‐type (WT) control mice were treated with OLZ, and changes in bloodglucose, serum and liver metabolites, whole‐body fuel oxidation, and pyruvate‐induced increases in blood glucose were measured. Additionally, WT mice were cotreated with OLZ and A769662, a specific AMPK β1 activator, and we determined if cotreatment protected against acute, OLZ‐induced metabolic dysfunction. OLZ‐induced increases in blood glucose were exacerbated in AMPK β1 ‐/‐ mice compared with WT mice, and this was paralleled by greater OLZ‐induced increases in markers of liver glucose production, such as pyruvate tolerance, serum glucagon, and glucagon responsiveness. Cotreatment with A769662 attenuated OLZ‐induced increases in blood glucose, serum nonesterified fatty acid, and glycerol. Furthermore, this effect was absent in AMPK β1 ‐/‐ mice, consistent with A769662's specificity for the AMPK β1 subunit. Reductions in AMPK activity potentiate the effects of acute OLZ treatment on blood glucose, whereas specifically targeting AMPK β1‐containing complexes is sufficient to protect against OLZ‐induced hyperglycemia.—Shamshoum, H., Medak, K. D., Townsend, L. K., Ashworth, K. E., Bush, N. D., Hahn, M. K., Kemp, B. E., Wright, D. C. AMPK β1 activation suppresses antipsychotic‐induced hyperglycemia in mice. FASEB J. 33, 14010‐14021 (2019). www.fasebj.org
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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) | 0.000 | 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) | 0.000 | 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".