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

• Published in: Journal of veterinary internal medicine 2011-03, Vol.25 (2), p.315-321
• Main Authors: Waller, A.P, Burns, T.A, Mudge, M.C, Belknap, J.K, Lacombe, V.A
• Format: Article
• Language: English
• Subjects: Animals; AS160; Biotinylated photo-affinity label; Female; glucose; Glucose Tolerance Test - veterinary; glucose tolerance tests; Glucose Transport Proteins, Facilitative - analysis; Glucose Transport Proteins, Facilitative - metabolism; Glucose Transporter Type 4 - analysis; Glucose Transporter Type 4 - metabolism; glucose transporters; GLUT (4 and 12) trafficking; Horse Diseases - metabolism; Horses - metabolism; humans; insulin; Insulin - pharmacology; Insulin Resistance; mares; medicine; Muscle, Skeletal - metabolism; muscles; protein synthesis; signal transduction; skeletal muscle; Western blotting
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/j.1939-1676.2010.0674.x

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.