• Open Access

Insulin Resistance Selectively Alters Cell-Surface Glucose Transporters but not their Total Protein Expression in Equine Skeletal Muscle


  • The work described herein was performed at The Ohio State University College of Pharmacy and College of Veterinary Medicine, Columbus, OH.

Corresponding author: Véronique A. Lacombe, College of Pharmacy, The Ohio State University, 500 W. 12th Avenue, Columbus, OH 43210; e-mail: lacombe.2@osu.edu.


Background: 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.

Hypothesis/Objectives: We hypothesized that cell-surface GLUT will be decreased in muscle by an AS160-dependent pathway in horses with IR.

Animals: 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 and Clinical Importance: IR induced defects in the skeletal muscle glucose transport pathway by decreasing active cell-surface GLUT4.