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.
Publication Date: 2011-02-11 PubMed ID: 21314720DOI: 10.1111/j.1939-1676.2010.0674.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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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
Researcher Affiliations
- College of Pharmacy, The Ohio State University, Columbus, OH, USA.
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
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