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J Vet Intern Med. 2011 Mar-Apr;25(2):315-21. doi: 10.1111/j.1939-1676.2010.0674.x. Epub 2011 Feb 11.

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

Author information

1
College of Pharmacy, The Ohio State University, Columbus, OH, USA.

Abstract

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.

PMID:
21314720
DOI:
10.1111/j.1939-1676.2010.0674.x
[Indexed for MEDLINE]
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