Microvascular Blood Flow Response to Hyperinsulinemia in Type 2 Diabetic Rats
Notice bibliographique
Résumé
Objective Chronic hyperglycemia is a defining feature of type 2 diabetes (T2D) that has been implicated in impaired microvascular structure and function. We aim to quantify the effect of hyperglycemia on local hemodynamic changes and spatial redistribution of blood flow in skeletal muscle capillary networks in response to hyperinsulinemia in an animal model of T2D. Methods Four 12‐week‐old Zucker Diabetic Fatty (ZDF) rats (2 lean, 2 obese) were fed a high fat diet (Purina 5008), acclimatized in animal quarters, and randomly selected on the day of experiment. Animals were anesthetized with sodium pentobarbital; cannulas were placed into the left common carotid and right jugular vein for systemic monitoring, anaesthetic administration and fluid resuscitation; animals were then tracheotomized and mechanically ventilated. Animals were maintained at 37□for the duration of the experiment and data collection. The right Extensor Digitorum Longus (EDL), a muscle of the lower‐hind limb, was isolated, and the distal tendon was cut to reflect the belly of the muscle over the objective of an Olympus IX‐73 microscope. Intravital videos of the microcirculation were recorded in 4–6 microscopic fields at multiple focal planes to capture blood flow in discrete capillary networks during baseline conditions. Euglycemia was achieved through intravenous infusion of insulin (2000 mU/kg/hr) and glucose (500 mg/kg/hr) until 3 stable blood glucose readings between 5 – 7 mM were made. Euglycemia was maintained while recordings were repeated in the same microscopic fields acquired during baseline. Results Resting blood glucose concentrations were 6.9 ± 0.4 mM for lean and 17.9 ± 1.2 mM for obese animals. At euglycemia, lean animals were brought to blood glucose levels of 6.3 ± 0.1 mM and obese to 6.2 ± 0.9 mM; mean glucose infusion rates were 28.9 ± 2.9 mg/kg/min for lean and 1.8 ± 2.1 mg/kg/min for obese animals. At baseline, mean capillary red blood cell (RBC) velocities were 233.0 ± 28.9 vs. 263.1 ± 24.2, hematocrits were 19.9 ± 4.3 vs. 32.9 ± 4.8, and RBC supply rates were 15.9 ± 1.3 vs. 21.9 ± 1.4 in lean and obese animals respectively (n = 525 capillaries). During hyperglycemia lean animals showed an 33% increase in RBC supply rate while obese animals showed a 25% decrease (n = 357 capillaries). Conclusion Hyperglycemia in control animals caused a marked increase in RBC supply rate in skeletal muscle tissue which may be an adaptive mechanism to enhance glucose uptake. This capillary flow response appears to be impaired in obese ZDF animals that share many characteristics with human T2D. Support or Funding Information This project was supported by a Medical Research Fund grant to GM Fraser from the Faculty of Medicine, Memorial University of Newfoundland. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».