The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae.
Abstract: An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance. Laminitis, failure of the weightbearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs), responsible for glucose uptake, is central to the dysregulation of glucose metabolism and may play a role in the pathophysiology of laminitis. Objective: We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our objectives were to compare the relative protein expression of major GLUT isoforms in striated muscle and digital lamellae in healthy horses and during marked and moderate hyperinsulinaemia. Methods: Randomised, controlled study. Methods: Prolonged hyperinsulinaemia and lamellar damage were induced by a prolonged euglycaemic-hyperinsulinaemic clamp or a prolonged glucose infusion, and results were compared with those of electrolyte-treated control animals. Protein expression of GLUTs was examined with immunoblotting. Results: Lamellar tissue contained more GLUT1 protein than skeletal muscle (P = 0.002) and less GLUT4 than the heart (P = 0.037). During marked hyperinsulinaemia and acute laminitis (induced by the prolonged euglycaemic-hyperinsulinaemic clamp), GLUT1 protein expression was decreased in skeletal muscle (P = 0.029) but unchanged in the lamellae, while novel GLUTs (8 and 12) were increased in the lamellae (P = 0.03) but not in skeletal muscle. However, moderate hyperinsulinaemia and subclinical laminitis (induced by the prolonged glucose infusion) did not cause differential GLUT protein expression in the lamellae compared with control horses. Conclusions: The results suggest that lamellar tissue functions independently of insulin and that insulin resistance may not be an essential component of the aetiology of laminitis. Marked differences in GLUT expression exist between insulin-sensitive and insulin-independent tissues during metabolic dysfunction in horses. The different expression profiles of novel GLUTs during acute and subclinical laminitis may be important to disease pathophysiology and require further investigation.
© 2014 EVJ Ltd.
Publication Date: 2014-09-10 PubMed ID: 24995680DOI: 10.1111/evj.12320Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the effect of prolonged high insulin levels on glucose transport in horses’ skeletal muscle and digital lamellae (tissues in the hooves), focusing on their relationship with laminitis, a painful condition in equines. The study compares the protein expression of glucose transporters in healthy horses and during periods of increased insulin levels.
Objective and Hypothesis
- The study was designed to compare the protein expression of major glucose transporter (GLUT) isoforms in the muscle and digital lamellae in healthy horses and during periods of high insulin levels.
- The hypothesis was that prolonged high insulin levels alter the regulation of glucose transport in insulin-sensitive tissue and digital lamellae, potentially contributing to laminitis.
Methodology
- The research was a randomized, controlled study. The prolonged hyperinsulinemia and lamellar damage in horses were induced either by a prolonged euglycaemic-hyperinsulinaemic clamp (a method that maintains blood glucose and insulin at constant, elevated levels) or a prolonged glucose infusion.
- The results were then compared with the control group – horses treated with electrolytes.
- Protein expression of GLUTs in the skeletal muscle and lamellae was examined with immunoblotting, a technique used to detect specific proteins.
Results
- Lamellae tissue showed more GLUT1 protein than skeletal muscle and less GLUT4 than the heart.
- During periods of high insulin and acute laminitis, the GLUT1 protein expression decreased in skeletal muscle but remained unchanged in the lamellae, while the expression of new GLUTs (8 and 12) increased in the lamellae but not in skeletal muscle.
- However, moderate hyperinsulinemia and subclinical laminitis did not result in differential GLUT protein expression in the lamellae compared to control horses.
Conclusions
- The findings suggest that lamellar tissue operates independently of insulin, leading to the conclusion that insulin resistance may not be a necessary element in the development of laminitis.
- Significant differences in GLUT expression were found between insulin-sensitive and insulin-independent tissues during metabolic dysfunction in horses. These different expression profiles of novel GLUTs during acute and subclinical laminitis could be critical to understanding the pathology of the disease and warrant further research.
Cite This Article
APA
de Laat MA, Clement CK, Sillence MN, McGowan CM, Pollitt CC, Lacombe VA.
(2014).
The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae.
Equine Vet J, 47(4), 494-501.
https://doi.org/10.1111/evj.12320 Publication
Researcher Affiliations
- Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, USA.
- Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, USA.
- Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Australia.
- Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Neston, UK.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Australia.
- Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, USA.
MeSH Terms
- Animals
- Gene Expression Regulation / physiology
- Glucose / metabolism
- Glucose Clamp Technique / veterinary
- Glucose Transport Proteins, Facilitative / genetics
- Glucose Transport Proteins, Facilitative / metabolism
- Horses / metabolism
- Hyperinsulinism / veterinary
- Muscle, Skeletal / metabolism
Citations
This article has been cited 7 times.- Vidal Moreno de Vega C, Lemmens D, de Meeûs d'Argenteuil C, Boshuizen B, de Maré L, Leybaert L, Goethals K, de Oliveira JE, Hosotani G, Deforce D, Van Nieuwerburgh F, Devisscher L, Delesalle C. Dynamics of training and acute exercise-induced shifts in muscular glucose transporter (GLUT) 4, 8, and 12 expression in locomotion versus posture muscles in healthy horses. Front Physiol 2023;14:1256217.
- Campolo A, Frantz MW, de Laat MA, Hartson SD, Furr MO, Lacombe VA. Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis. Front Vet Sci 2020;7:308.
- Watts MR, Hegedus OC, Eades SC, Belknap JK, Burns TA. Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light-breed horses. J Vet Intern Med 2019 May;33(3):1483-1492.
- Bertin FR, Taylor SD, Bianco AW, Sojka-Kritchevsky JE. The Effect of Fasting Duration on Baseline Blood Glucose Concentration, Blood Insulin Concentration, Glucose/Insulin Ratio, Oral Sugar Test, and Insulin Response Test Results in Horses. J Vet Intern Med 2016 Sep;30(5):1726-1731.
- Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Concentration Dependent Influence of Lipopolysaccharides on Separation of Hoof Explants and Supernatant Lactic Acid Concentration in an Ex Vivo/In Vitro Laminitis Model. PLoS One 2015;10(11):e0143754.
- Jackson EE, Rendina-Ruedy E, Smith BJ, Lacombe VA. Loss of Toll-Like Receptor 4 Function Partially Protects against Peripheral and Cardiac Glucose Metabolic Derangements During a Long-Term High-Fat Diet. PLoS One 2015;10(11):e0142077.
- Valberg SJ, Velez-Irizarry D, Williams ZJ, Pagan JD, Mesquita V, Waldridge B, Maresca-Fichter H. Novel Expression of GLUT3, GLUT6 and GLUT10 in Equine Gluteal Muscle Following Glycogen-Depleting Exercise: Impact of Dietary Starch and Fat. Metabolites 2023 Jun 1;13(6).
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