FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary internal medicine2011; 25(2); 315-321; doi: 10.1111/j.1939-1676.2010.0674.x

Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle.

Abstract: Insulin resistance (IR) has been widely recognized in humans, and more recently in horses, but its underlying mechanisms are still not well understood. The translocation of glucose transporter 4 (GLUT4) to the cell surface is the limiting step for glucose uptake in insulin-sensitive tissues. Although the downstream signaling pathways regulating GLUT translocation are not well defined, AS160 recently has emerged as a potential key component. In addition, the role of GLUT12, one of the most recently identified insulin-sensitive GLUTs, during IR is unknown. Objective: We hypothesized that cell-surface GLUT will be decreased in muscle by an AS160-dependent pathway in horses with IR. Methods: Insulin-sensitive (IS) or IR mares (n = 5/group). Methods: Muscle biopsies were performed in mares classified as IS or IR based on results of an insulin-modified frequently sampled IV glucose tolerance test. By an exofacial bis-mannose photolabeled method, we specifically quantified active cell-surface GLUT4 and GLUT12 transporters. Total GLUT4 and GLUT12 and AS160 protein expression were measured by Western blots. Results: IR decreased basal cell-surface GLUT4 expression (P= .027), but not GLUT12, by an AS160-independent pathway, without affecting total GLUT4 and GLUT12 content. Cell-surface GLUT4 was not further enhanced by insulin stimulation in either group. Conclusions: IR induced defects in the skeletal muscle glucose transport pathway by decreasing active cell-surface GLUT4.
Copyright © 2011 by the American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2011-02-11 PubMed ID: 21314720DOI: 10.1111/j.1939-1676.2010.0674.xGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates how insulin resistance (IR) affects the activity of glucose transporters in equine skeletal muscles. More specifically, it looks at the effects of IR on the translocation of glucose transporter 4 (GLUT4) and GLUT12 to the muscle cell surface, hypothesizing a decrease in these transporters due to an AS160-dependent pathway in horses with IR.

Objective

This study was designed to explore the impact of insulin resistance (IR) on glucose transporter proteins (GLUT4 and GLUT12) in horses. Insulin resistance is a condition that impairs the body’s ability to effectively use insulin, often leading to diabetes. This study hypothesized that IR would reduce the number of these GLUTs at the cell surface due to a pathway that involves the protein AS160, a key component in the signaling pathways regulating GLUT translocation.

Methods

  • The researchers first classified horses as either insulin-sensitive (IS) or insulin-resistant (IR) based on an insulin-modified frequently sampled IV glucose tolerance test.
  • They then performed muscle biopsies on these horses, allowing them to study the muscle tissues directly.
  • Using a method called exofacial bis-mannose photolabeling, they were able to specifically measure the active cell-surface GLUT4 and GLUT12 transporter proteins.
  • A technique called Western blotting was used to measure total GLUT4 and GLUT12 transporter proteins, as well as AS160 protein expression.

Results

  • The research showed that insulin resistance led to a decrease in active cell-surface GLUT4 proteins, but not GLUT12.
  • This reduction appeared to occur through an AS160-independent pathway, contrary to the researchers’ initial hypothesis.
  • Total expression of GLUT4 and GLUT12 proteins did not change, implying that insulin resistance does not affect their overall production but it impacts their presence at the muscle cell surface.

Conclusions

Based on these findings, it seems that insulin resistance (IR) brings about dysfunction in the skeletal muscle glucose transport pathway by reducing the active cell-surface GLUT4 proteins. This finding contributes to the understanding of how IR affects glucose metabolism and could provide insights to develop effective therapeutic interventions.

Cite This Article

APA
Waller AP, Burns TA, Mudge MC, Belknap JK, Lacombe VA. (2011). Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle. J Vet Intern Med, 25(2), 315-321. https://doi.org/10.1111/j.1939-1676.2010.0674.x

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 25
Issue: 2
Pages: 315-321

Researcher Affiliations

Waller, A P
  • College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Burns, T A
    Mudge, M C
      Belknap, J K
        Lacombe, V A

          MeSH Terms

          • Animals
          • Female
          • Glucose Tolerance Test / veterinary
          • Glucose Transport Proteins, Facilitative / analysis
          • Glucose Transport Proteins, Facilitative / metabolism
          • Glucose Transporter Type 4 / analysis
          • Glucose Transporter Type 4 / metabolism
          • Horse Diseases / metabolism
          • Horses / metabolism
          • Insulin / pharmacology
          • Insulin Resistance
          • Muscle, Skeletal / metabolism

          Grant Funding

          • K01RR023083-01 / NCRR NIH HHS

          Citations

          This article has been cited 23 times.
          1. 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.
            doi: 10.3389/fphys.2023.1256217pubmed: 37654675google scholar: lookup
          2. Loos CMM, McLeod KR, Vanzant ES, Stratton SA, Bohannan AD, Coleman RJ, van Doorn DA, Urschel KL. Differential effect of two dietary protein sources on time course response of muscle anabolic signaling pathways in normal and insulin dysregulated horses. Front Vet Sci 2022;9:896220.
            doi: 10.3389/fvets.2022.896220pubmed: 35978710google scholar: lookup
          3. Huang Q, Huang Y, Liu J. Mesenchymal Stem Cells: An Excellent Candidate for the Treatment of Diabetes Mellitus. Int J Endocrinol 2021;2021:9938658.
            doi: 10.1155/2021/9938658pubmed: 34135959google scholar: lookup
          4. Kępczyński Ł, Wcisło S, Korzeniewska-Dyl I, Połatyńska K, Gach A, Moczulski D. No evidence for change in expression of TBC1D1 and TBC1D4 genes in cultured human adipocytes stimulated by myokines and adipokines. Adipocyte 2021 Dec;10(1):153-159.
            doi: 10.1080/21623945.2021.1900497pubmed: 33769190google scholar: lookup
          5. Li G, Peng H, Qian S, Zou X, Du Y, Wang Z, Zou L, Feng Z, Zhang J, Zhu Y, Liang H, Li B. Bone Marrow-Derived Mesenchymal Stem Cells Restored High-Fat-Fed Induced Hyperinsulinemia in Rats at Early Stage of Type 2 Diabetes Mellitus. Cell Transplant 2020 Jan-Dec;29:963689720904628.
            doi: 10.1177/0963689720904628pubmed: 32228047google scholar: lookup
          6. Klein DJ, McKeever KH, Mirek ET, Anthony TG. Metabolomic Response of Equine Skeletal Muscle to Acute Fatiguing Exercise and Training. Front Physiol 2020;11:110.
            doi: 10.3389/fphys.2020.00110pubmed: 32132934google scholar: lookup
          7. Shoop S, Maria Z, Campolo A, Rashdan N, Martin D, Lovern P, Lacombe VA. Glial Growth Factor 2 Regulates Glucose Transport in Healthy Cardiac Myocytes and During Myocardial Infarction via an Akt-Dependent Pathway. Front Physiol 2019;10:189.
            doi: 10.3389/fphys.2019.00189pubmed: 30971932google scholar: lookup
          8. Zhao P, Ming Q, Qiu J, Tian D, Liu J, Shen J, Liu QH, Yang X. Ethanolic Extract of Folium Sennae Mediates the Glucose Uptake of L6 Cells by GLUT4 and Ca(2). Molecules 2018 Nov 9;23(11).
            doi: 10.3390/molecules23112934pubmed: 30424024google scholar: lookup
          9. Maria Z, Campolo AR, Lacombe VA. Diabetes Alters the Expression and Translocation of the Insulin-Sensitive Glucose Transporters 4 and 8 in the Atria. PLoS One 2015;10(12):e0146033.
            doi: 10.1371/journal.pone.0146033pubmed: 26720696google scholar: lookup
          10. 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.
            doi: 10.1371/journal.pone.0142077pubmed: 26539824google scholar: lookup
          11. Banse HE, Frank N, Kwong GP, McFarlane D. Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses. Can J Vet Res 2015 Oct;79(4):329-38.
            pubmed: 26424915
          12. Lacombe VA. Expression and regulation of facilitative glucose transporters in equine insulin-sensitive tissue: from physiology to pathology. ISRN Vet Sci 2014;2014:409547.
            doi: 10.1155/2014/409547pubmed: 24977043google scholar: lookup
          13. Ertelt A, Barton AK, Schmitz RR, Gehlen H. Metabolic syndrome: is equine disease comparable to what we know in humans?. Endocr Connect 2014 Sep;3(3):R81-93.
            doi: 10.1530/EC-14-0038pubmed: 24894908google scholar: lookup
          14. Song X, Lichti CF, Townsend RR, Mueckler M. Single point mutations result in the miss-sorting of Glut4 to a novel membrane compartment associated with stress granule proteins. PLoS One 2013;8(7):e68516.
            doi: 10.1371/journal.pone.0068516pubmed: 23874650google scholar: lookup
          15. Pujol-Giménez J, Barrenetxe J, González-Muniesa P, Lostao MP. The facilitative glucose transporter GLUT12: what do we know and what would we like to know?. J Physiol Biochem 2013 Jun;69(2):325-33.
            doi: 10.1007/s13105-012-0213-8pubmed: 23385668google scholar: lookup
          16. Si Y, Zhao Y, Hao H, Liu J, Guo Y, Mu Y, Shen J, Cheng Y, Fu X, Han W. Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes 2012 Jun;61(6):1616-25.
            doi: 10.2337/db11-1141pubmed: 22618776google scholar: lookup
          17. Waller AP, Kohler K, Burns TA, Mudge MC, Belknap JK, Lacombe VA. Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation. Biochim Biophys Acta 2011 Sep;1812(9):1098-103.
            doi: 10.1016/j.bbadis.2011.02.007pubmed: 21352908google scholar: lookup
          18. Lin FM, Xu JH, Shen CH, Wu ST, Chu TW. Diagnostic Potential of Volatile Organic Compounds in Detecting Insulin Resistance Among Taiwanese Women. Diagnostics (Basel) 2025 Jul 18;15(14).
            doi: 10.3390/diagnostics15141817pubmed: 40722566google scholar: lookup
          19. Kim JE, Lee JW, Cha GD, Yoon JK. The Potential of Mesenchymal Stem Cell-Derived Exosomes to Treat Diabetes Mellitus. Biomimetics (Basel) 2025 Jan 14;10(1).
            doi: 10.3390/biomimetics10010049pubmed: 39851765google scholar: lookup
          20. Fresa K, Catandi GD, Whitcomb L, Gonzalez-Castro RA, Chicco AJ, Carnevale EM. Adiposity in mares induces insulin dysregulation and mitochondrial dysfunction which can be mitigated by nutritional intervention. Sci Rep 2024 Jun 18;14(1):13992.
            doi: 10.1038/s41598-024-64628-xpubmed: 38886475google scholar: lookup
          21. Campolo A, Maria Z, Lacombe VA. Diabetes Causes Significant Alterations in Pulmonary Glucose Transporter Expression. Metabolites 2024 May 7;14(5).
            doi: 10.3390/metabo14050267pubmed: 38786744google scholar: lookup
          22. Burgos M, Gil-Iturbe E, Idoate-Bayón A, Castilla-Madrigal R, Moreno-Aliaga MJ, Lostao MP. The glucose transporter GLUT12, a new actor in obesity and cancer. J Physiol Biochem 2025 May;81(2):391-401.
            doi: 10.1007/s13105-024-01028-9pubmed: 38727993google scholar: lookup
          23. 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).
            doi: 10.3390/metabo13060718pubmed: 37367876google scholar: lookup
          Subscribe to our newsletter
          Join 99,970 horse owners like you who receive our email updates on horse health and nutrition.