Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses

Gauff, Felicia C.; Patan-Zugaj, Bianca; Licka, Theresia

doi:10.2460/ajvr.75.4.367

Cited by 3 publications

(3 citation statements)

References 34 publications

(61 reference statements)

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“…A study by Gauff et al . (122) indicated that localization and expression of ETRA and ETRB varied within lamellar tissue of the equine forelimb. The results of the study suggested that the vasoconstrictive effect of hyperinsulinemia is caused primarily by activation of ETRA located in smooth muscle of blood vessels (122) .…”

Section: Pathophysiology Of Metabolic Syndromementioning

confidence: 98%

Metabolic syndrome: is equine disease comparable to what we know in humans?

Ertelt¹,

Barton²,

Schmitz³

et al. 2014

Endocrine Connections

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This review summarizes similarities and differences between the metabolic syndromes in humans and equines, concerning the anatomy, symptoms, and pathophysiological mechanisms. In particular, it discusses the structure and distribution of adipose tissue and its specific metabolic pathways. Furthermore, this article provides insights and focuses on issues concerning laminitis in horses and cardiovascular diseases in humans, as well as their overlap.

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Section: Pathophysiology Of Metabolic Syndromementioning

confidence: 98%

Metabolic syndrome: is equine disease comparable to what we know in humans?

Ertelt¹,

Barton²,

Schmitz³

et al. 2014

Endocrine Connections

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“…Among other possible mechanisms that could disrupt lamellar epithelial cell homeostasis, disturbances of perfusion and energy metabolism have been frequently implicated in endocrinopathic laminitis . Previous studies have focused on how insulin resistance (or hyperinsulinaemia itself) may cause endothelial dysfunction and lamellar vasoconstriction and treatments to enhance digital perfusion have been investigated and advocated for the prevention and treatment of laminitis .…”

Section: Introductionmentioning

confidence: 99%

“…10 Among other possible mechanisms that could disrupt lamellar epithelial cell homeostasis, disturbances of perfusion and energy metabolism have been frequently implicated in endocrinopathic laminitis. [12][13][14][15] Previous studies have focused on how insulin resistance (or hyperinsulinaemia itself) may cause endothelial dysfunction and lamellar vasoconstriction 13,15,16 and treatments to enhance digital perfusion have been investigated and advocated for the prevention and treatment of laminitis. [17][18][19][20] Although adequate glucose availability is critical to the maintenance of lamellar structure and function, 21 ischaemic or non-ischaemic disturbances of glucose metabolism, or other alterations of lamellar energy balance have not been demonstrated during endocrinopathic laminitis development.…”

Section: Introductionmentioning

confidence: 99%

Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis

Stokes

Bertin

Stefanovski

et al. 2020

Equine Veterinary Journal

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Background Hyperinsulinaemia is associated with the development of endocrinopathic laminitis; however, the mechanisms remain unclear. Objectives Evaluate the effects of hyperinsulinaemia on lamellar energy metabolism and perfusion during laminitis development. Study design In vivo experiment. Methods Eight Standardbred horses were instrumented with a microdialysis probe in the lamellae of a forelimb. A 24 hours baseline period (BASELINE) was followed by 48 hours of a continuous euglycaemic hyperinsulinaemic clamp (EHC) from 24 to 72 hours (CLAMP). Microdialysate was collected every 6 hours and analysed for glucose, lactate and pyruvate concentrations and lactate‐to‐pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar tissue perfusion. Archived microdialysis samples from six identically instrumented Standardbred horses served as controls (CON). Variables were compared over time and between EHC and CON horses using a mixed‐effects linear regression model. Results Glucose concentration decreased during the CLAMP period in CON and EHC horses (P < .001), but there was no difference between CON and EHC (P > .9). Lactate concentration increased during the CLAMP period in CON and EHC horses (P < .001), however, the rate of increase was significantly higher in EHC horses relative to CON (P = .014). There was a relative increase in pyruvate concentration in EHC horses compared with CON during the CLAMP period (P = .03). L:P increased significantly in CON horses during the CLAMP period (P < .001) but not in EHC (P = .1). Urea clearance did not change in CON (P = .9) or EHC (P = .05) during the CLAMP, but did increase in EHC relative to CON (P = .02). Main limitations The effects of microdialysis probe implantation on perfusion and metabolism remain unclear. The EHC model may not mimic natural endocrinopathic laminitis. Conclusions Laminitis developed without evidence of lamellar hypoperfusion or energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis.

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Establishment of a model for equine small intestinal disease: effects of extracorporeal blood perfusion of equine ileum on metabolic variables and histological morphology – an experimental ex vivo study

et al. 2019

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BackgroundIn horses a number of small intestinal diseases is potentially life threatening. Among them are Equine Grass Sickness (EGS), which is characterised by enteric neurodegeneration of unknown aetiology, as well as reperfusion injury of ischaemic intestine (I/R), and post-operative ileus (POI), common after colic surgery. The perfusion of isolated organs is successfully used to minimize animal testing for the study of pathophysiology in other scenarios. However, extracorporeal perfusion of equine ileum sourced from horses slaughtered for meat production has not yet been described. Therefore the present study evaluated the potential of such a model for the investigation of small intestinal diseases in an ex vivo and cost-efficient system avoiding experiments in live animals.ResultNine ileum specimens were sourced from horses aged 1–10 years after routine slaughter at a commercial abattoir. Ileum perfusion with oxygenated autologous blood and plasma was successfully performed for 4 h in a warm isotonic bath (37.0–37.5 °C). Ileum specimens had good motility and overall pink to red mucosa throughout the experiment; blood parameters indicated good tissue vitality: 82 ± 34 mmHg mean arterial partial pressure of oxygen (pO2) compared to 50 ± 17 mmHg mean venous pO2, 48 ± 10 mmHg mean arterial partial pressure of carbon dioxide (pCO2) compared to 66 ± 7 mmHg venous pCO2 and 9.8 ± 2.8 mmol/L mean arterial lactate compared to 11.6 ± 2.7 mmol/L venous lactate. There was a mild increase in ileum mass reaching 105 ± 7.5% of the pre-perfusion mass after 4 hours. Histology of haematoxylin and eosin stained biopsy samples taken at the end of perfusion showed on average 99% (±1%) histologically normal neurons in the submucosal plexus and 76.1% (±23.9%) histologically normal neurons in the myenteric plexus and were not significantly different to control biopsies.ConclusionExtracorporeal, normothermic perfusion of equine ileum over 4 h using autologous oxygenated blood/plasma perfusate showed potential as experimental model to test whether haematogenous or intestinal exposure to neurotoxins suspected in the pathogenesis of EGS can induce neuronal damage typical for EGS. Also, this model may allow investigations into the effect of pharmaceuticals on I/R injury, as well as into the pathogenesis of equine POI.

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Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses

Abstract: Hyperinsulinemia caused significant changes in endothelin receptor expression, which suggested that ETR antagonists might be beneficial for treatment of laminitis in horses.

Cited by 3 publications

References 34 publications

Metabolic syndrome: is equine disease comparable to what we know in humans?

Metabolic syndrome: is equine disease comparable to what we know in humans?

Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis

Establishment of a model for equine small intestinal disease: effects of extracorporeal blood perfusion of equine ileum on metabolic variables and histological morphology – an experimental ex vivo study

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