7A.02
Bibliographic record
Abstract
Objective: Obesity and diabetes enhance the risk of developing cardiovascular diseases and heart failure. The heart/cardiac oxytocin (OT) system was discovered by our group and shown to regulate cardiovascular cell survival pathways and cardioprotection. OT is also involved in the regulation of cardiac energy metabolism and cardiac OT receptor is downregulated in diabetes. Our hypothesis is that OT prevents development of diabetic cardiomyopathy. We evaluated whether chronic treatment with OT could prevent the metabolic and cardiac abnormalities associated with diabetes and obesity using the db/db mice. Design and method: Four-week-old C57BL/KsJ-db/db obese diabetic mice (db/db) and their lean control littermates (db/+) were treated with OT (125 ng/kg/h) or saline during 12 weeks (n = 10/group). Serial blood and tomography analysis were performed. Cardiac function was determined by echocardiography, and biochemical and histological heart and fat analysis were also performed. Results: Compared to db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia and hyperinsulinemia. These mice also exhibited a deficient cardiac OT/natriuretic system and developed systolic and diastolic dysfunction resulting from cardiomyocytes hypertrophy, fibrosis and apoptosis. These abnormalities were associated with increased ROS production, inflammation and suppressed AMP-kinase signaling pathway. The db/db mice displayed reduced serum levels of adiponectin and adipsin and elevated resistin. OT treatment increased circulating OT levels, significantly reduced serum resistin, body fat accumulation (19%: p < 0.001), fasting blood glucose levels by (23%; p < 0.001), and improved glucose tolerance and insulin sensitivity. OT also normalized cardiac OT receptors, ANP and BNP expressions and prevented systolic and diastolic dysfunction as well as cardiomyocytes hypertrophy, fibrosis and apoptosis. Furthermore, OT reduced cardiac oxidative stress and inflammation, and normalized the AMP-activated protein kinase signaling pathway. The complete normalization of cardiac structure and function by OT treatment in db/db mice contrasted with only partial improvement of hyperglycemia and hyperinsulinemia. Conclusions: The results indicate that chronic treatment with OT partially improves glucose and fat metabolism, reverses abnormal cardiac structural remodeling, preventing cardiac dysfunction in db/db mice. These observations clearly suggest a potential role for OT in replacement therapy for the prevention of cardiovascular complications of diabetes and obesity.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.006 | 0.002 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.898 | 0.901 |
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".