Pre‐diabetes promotes sympathetically‐mediated arteriolar dysregulation in response to skeletal muscle contraction (676.20)
Bibliographic record
Abstract
Augmented sympathetic vascular regulation is associated with pre‐diabetes, thus it may contribute to impaired contraction‐evoked arteriolar dilation in skeletal muscle, previously demonstrated by our group. Thus we tested the hypothesis that blunted contraction‐evoked arteriolar dilation in pre‐diabetes occurs as a result of augmented sympathetic neuropeptide Y1 receptor (NPY Y1R) and α1 adrenergic receptor (α1R) control. Using intravital video microscopy, second‐ third‐ and fourth‐order arteriolar diameter changes were measured in response to electrical field stimulation of the gluteus maximus muscle in pre‐diabetic (PD, Pound Mouse, n=6‐13) and control (CTRL, c57bl6, CTRL, n=5‐12) mice. Baseline diameter was similar between groups, however vasodilatory responses to single tetanic (100Hz; 400 and 800ms) and sustained rhythmic (2 and 8Hz; 30s) contractions were blunted by 50% or greater in PD versus CTRL (p<0.05). In line with our hypothesis, decrements in contraction‐evoked dilation in PD were restored upon Y1R and α1R blockade (BIBP3226 and prazosin, 100nM). Arteriolar reactivity (% change from baseline diameter) to muscle contraction was greatest at distal arterioles in CTRL. Such spatial differences in arteriolar reactivity were absent in PD, but were restored with Y1R and α1R blockade. Finally, arteriolar vasoconstrictor responses to increasing doses of NPY (10‐13 ‐ 10‐8 M) or PE (10‐9 M ‐ 10‐5 M) were greater in PD versus CTRL, an observation that was consistent with greater Y1R and α1R expression in isolated arterioles and vascular smooth muscle cells in PD. Deficits in contraction‐evoked arteriolar dilation in this model of pre‐diabetes are a result of elevated sympathetic arteriolar Y1R and α1R expression and activation. Grant Funding Source : NSERC
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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) | 0.000 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".