Microvascular Blood Flow Response to Hyperinsulinemic‐Euglycemic Clamp in Zucker Diabetic Sprague Dawley Rat Model of Type 2 Diabetes
Notice bibliographique
Résumé
Objective Quantify and characterize the skeletal muscle microvascular blood flow in Zucker Diabetic Sprague Dawley (ZDSD) rat model of T2D at rest and during a hyperinsulinemic‐euglycemic clamp. Hypothesis Chronic hyperglycemia in the ZDSD rat model of T2D causes blunted capillary hemodynamic response to hyperinsulinemic‐euglycemic clamp compared to the age and diet matched control Sprague Dawley (SD) rats. Methods Biweekly blood glucose and conscious blood pressure measurements were collected from 7‐ to 25‐week‐old male SD (n=12) and ZDSD (n=18) rats. At 27 weeks of age, animals were fasted overnight prior to intravital video microscopy experiments. On the day of experiment animals were anaesthetized with an intraperitoneal injection of pentobarbital, tracheotomized, and carotid and external jugular cannulas were inserted to monitor physiological status and for administration of fluids. The extensor digitorum longus (EDL) muscle of the lower hind limb was isolated, blunt dissected and reflected over a glass coverslip on the stage of an inverted microscope. Recordings of the EDL were completed at baseline and during hyperinsulinemic‐euglycemic clamp. Hyperinsulinemic‐euglycemic clamp was achieved by continuous intravenous infusion of insulin (Humulin R 2U/hr/kg) and a 50% glucose mixture to titrate blood glucose to euglycemia (5‐7 mM). Mixed blood samples were collected from a tail clip to determine systemic blood glucose. Analysis of intravital videos were completed offline using custom MATLAB software. ZDSD rats that had fasting blood glucose of less than 20 mM at 19 weeks of age were excluded from the hyperglycemic group. Animals exhibiting aberrant microvascular blood flow at baseline or during euglycemic clamp were excluded from the data set. All animal protocols were approved by Memorial University of Newfoundland’s Animal Care and Use Committee. Results Hyperglycemic ZDSD rats had a significantly higher blood glucose than SD controls from 17 to 25 weeks old and at the beginning of euglycemic clamp (26.13 ± 0.97 and 5.95 ± 0.37, p < 0.0001, Fig 1A). SD rats had a significantly higher glucose infusion rate than ZDSD rats (22.58 ± 1.81 and 13.19 ± 2.76, p < 0.0001, Fig 1B). SD rats had a significant increase in red blood cell (RBC) velocity (149.8 ± 56.71 and 210.0 ± 62.14 µm/s, p = 0.0051, Fig 2A), RBC supply rate (SR) (12.49 ± 8.23 and 19.91 ± 12.25 cells/s, p = 0.004, Fig 2B) and RBC oxygen saturation(sO 2 ) (38.05 ± 11.65 and 45.70 ± 10.13, p = 0.014, Fig 2D) between baseline and euglycemia. However, ZDSD animals had no significant difference in RBC velocity (178.1 ± 63.91 and 194.7 ± 37.69 µm/s, p = 0.3683, Fig 2A), RBC supply rate (14.63 ± 7.55 and 20.03 ± 7.46 cells/s, p = 0.0704, Fig 2B), hematocrit (31.03 ± 3.23 and 33.02 ± 6.22 %, p = 0.4309, Fig 2C), and RBC sO 2 (61.91 ± 11.40 and 64.00 ± 11.59, p = 0.5324 Fig 2D). The RBC sO 2 was significantly higher in ZDSD than SD at baseline (61.91 ± 11.40 compared to 38.05 ± 11.65, p = 0.0166, Fig 2D). Conclusion SD rats had a robust increase in capillary hemodynamics during hyperinsulinemic‐euglycemic clamp. However, the skeletal muscle capillary hemodynamics of ZDSD rats did not significantly change between baseline and during euglycemia. These finding suggests a potential impairment in skeletal muscle microvascular blood flow response in this type 2 diabetic rodent mode. The elevated RBC sO 2 in ZDSD rats may indicate a dysregulation of capillary blood flow in the ZDSD model.
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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 ».