Receptor Binding Profiles of Antipsychotic Medications and Glucose Dysregulation: An Acute Animal Model
Bibliographic record
Abstract
Atypical antipsychotics (AAPs) are associated with metabolic sequelae including risk of type 2 diabetes. Evidence points to a weight-gain independent and direct drug effect on glucose homeostasis. While the exact mechanisms remain elusive, the heterogeneous binding profiles of AAPs likely include receptors involved in glucose metabolism. We aimed to clarify weight-gain independent mechanisms of AAP-induced alterations in insulin secretion. Deconstruction of the receptor binding profiles of these agents was done using representative antagonists and the hyperglycemic clamp. We assessed the acute effects of several selective receptor antagonists on glucose metabolism, namely prazosin, idazoxan, MDL100907, SB242084 and WAY100635. Prazosin and MDL100907, selective α1 and 5HT2A antagonists, respectively, caused significant decreases in both insulin and C-peptide secretion. A decreased glucose infusion rate and disposition index was also found in the prazosin group. Antagonism of the α1 and 5HT2A receptors may be involved in AAP-induced glucose dysregulation, however, the responsible mechanisms remain unknown.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 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".