Insulin‐Mediated Vasodilation in Cerebral Arteries is Impaired in Obese Rats with Type 2 Diabetes
Bibliographic record
Abstract
Insulin stimulates resistance artery vasodilation in skeletal muscle and the brain. Type 2 diabetes (T2D) attenuates insulin‐induced vasodilation in skeletal muscle arteries, but whether this adaptation occurs in the cerebrovasculature and is related to impaired cognition remains to be elucidated. This study tested the hypothesis that cognition and insulin‐mediated vasodilation in the cerebrovasculature were impaired in obese rats with type 2 diabetes. Eight week old hyperphagic, Otsuka Long Evans Tokushima Fatty rats were divided into two groups; food controlled (CON, n=8) and free food access (model of T2D, n=8). Cognition was measured monthly using a Barnes maze for 4 months (i.e. at 8, 12, 16 and 20 wk of age) prior to vascular testing. At 20 wk of age, rats underwent a euglycemic hyperinsulinemic clamp, while carotid artery blood flow (BF; perivascular flow probe) and mean arterial pressure (MAP; arterial catheter) were measured. Thereafter, rats were decapitated, their cerebral arteries were isolated, and vasomotor responses (pressurized myography) to graded increases in intraluminal pressure (40–140 mmHg) and exogenous insulin (1–10000 uIU) were assessed in untreated and endothelin‐1 inhibition (BQ123) conditions. Results indicate that cognition improved over time, but was not different between groups at any time point. Carotid BF, MAP and vascular conductance (BF/MAP) were also not different between groups and did not change during the insulin clamp. Prior to and following the development of spontaneous tone, absolute diameter of the cerebral arteries was not different between groups. Vasomotor tone increased similarly in both groups during graded increases in intraluminal pressure (40–140 mmHg; P<0.05). Insulin‐mediated vasodilation (at 80 mmHg pressure) was attenuated in the T2D vs. CON (peak dilation = ~10 % vs. 30%; P<0.05). Endothelin‐1 inhibition restored insulin‐mediated vasodilation in the T2D group. A priori pairwise comparison between the cumulative average percent possible insulin‐mediated vasodilation in the untreated vs. endothelin‐1 inhibition conditions revealed that endothelin‐1 significantly restrained insulin‐mediated vasodilation in the T2D, but not the CON group (P<0.05). Thus, at this stage in development of T2D (~20 wk is the onset in this model), cognition, and cranial flow at rest and during an insulin clamp appear unaffected; even though isolated cerebral arteries exhibit vascular insulin resistance. These data from isolated cerebral arteries support the notion that impaired insulin‐mediated cerebral vasodilation in T2D is the result of enhanced insulin‐stimulated endothelin‐1 production. Support or Funding Information College of Veterinary Medicine, University of Missouri‐Columbia
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".