Metformin treatment corrects vascular insulin resistance in hypertension
Bibliographic record
Abstract
OBJECTIVE: In states of insulin resistance, the vasorelaxant actions of insulin are blunted, which may contribute towards the development of increased vascular tone/hypertension and reduced glucose uptake. To examine whether treating insulin resistance in hypertension restores the vascular actions of insulin, we studied the long-term effects of metformin on the contractile responses of isolated aortas from control and insulin-resistant, hyperinsulinaemic fructose-hypertensive rats in the presence and absence of insulin. DESIGN AND METHODS: Sprague Dawley rats were divided into control, control metformin-treated, fructose and fructose metformin-treated groups (n = 8 per group). The treated groups received metformin (500 mg/kg per day for 6 weeks), following which isometric responses to noradrenaline (NA) and angiotensin II (A-II) were examined in thoracic aortas in the presence and absence of insulin (100 mU/ml for 2 h) using isolated organ-bath apparatus. In addition, endothelium-dependent and independent vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were also studied. RESULTS: Metformin treatment prevented the development of fructose-induced insulin resistance, hyperinsulinaemia and hypertension. Insulin attenuated the contractile responses to NA and A-II in control rat aortas; however, blood vessels from untreated fructose rats were refractory to insulin-induced vasodilation. Strikingly, long-term metformin treatment restored the vasodepressor actions of insulin in fructose rats. Metformin did not affect the contractile responses to NA or A-II in either control or fructose rats. In addition, metformin treatment restored ACh-induced endothelium-dependent vasorelaxation in aortas from fructose rats without affecting SNP-induced relaxation. CONCLUSIONS: These data show, for the first time, that long-term metformin treatment corrects vascular insulin resistance and improves endothelium-dependent vasorelaxation in hypertension. These effects appear to be secondary to metformin-induced improvements in metabolic derangements (versus a direct vascular action of metformin). Improving the vascular effects of insulin may serve to decrease peripheral tone, attenuate blood pressure and improve insulin sensitivity.
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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) | 0.001 | 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".