Increasing Peripheral Insulin Sensitivity by Protein Tyrosine Phosphatase 1B Deletion Improves Control of Blood Pressure in Obesity
Bibliographic record
Abstract
Obesity is a major risk factor for hypertension. The copresentation of hypertension and insulin resistance (IR) suggests a role for IR in blood pressure (BP) dysregulation. To test this hypothesis, peripheral IR has been genetically subtracted in a model of obesity by crossing leptin receptor mutant mice (K(db)H(PTP)) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, H(db)K(PTP)) to generate obese insulin-sensitive mice (K(db)K(PTP)). BP was recorded in lean (H(db)H(PTP), H(db)K(PTP)) and obese (K(db)H(PTP), K(db)K(PTP)) mice via telemetry, and a frequency analysis of the recording was performed to determine BP variability. Correction of IR in obese mice normalized BP values to baseline levels (H(db)H(PTP): 116 ± 2 mm Hg; K(db)H(PTP): 129 ± 4 mm Hg; K(db)K(PTP): 114 ± 5 mm Hg) and restored BP variability by decreasing its standard deviation and the frequency of BP values over the upper autoregulatory limit of the kidneys. However, although IR-induced increases in proteinuria (versus 53 ± 13 μg/d, H(db)H(PTP)) were corrected in K(db)K(PTP) (112 ± 39 versus 422 ± 159 μg/d, K(db)H(PTP)), glomerular hypertrophy was not. IR reduced plasma aldosterone levels ruling out a role for mineralocorticoids in the development of hypertension. Taken together, these data indicate that correction of IR prevents hypertension, BP variability, and microalbuminuria in obese mice. Although the mechanism remains to be fully determined, increases in aldosterone or sympathoactivation of the cardiovascular system seem to be less likely contributors.
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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 | 0.001 | 0.001 |
| 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".