Microvascular Blood Flow Response to Hyperinsulinemia in Type 2 Diabetic Rats
Bibliographic record
Abstract
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 .
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".