Insulin sensitivity and skeletal muscle glucose transport in horses with equine polysaccharide storage myopathy.
Equine polysaccharide storage myopathy (PSSM) is an inherited disorder characterized by the accumulation of glycogen and abnormal polysaccharide in muscle with normal glyco(geno)lytic enzyme activities. The purpose of this study was to evaluate in vivo insulin sensitivity and glucose excursion in PSSM using a euglycemic hyperinsulinemic clamp. In addition, the content of muscle glucose transporters (GLUT1 and GLUT4) and the insulin receptor was determined in muscle biopsies using Western blot analysis. The glycogen content was 1.8-fold higher, and isolated polysaccharide analyzed by iodine absorption spectra, was less branched in equine PSSM. Throughout the clamp, the affected horses required a higher rate of glucose infusion to maintain euglycemia. Although GLUT1 content was lower, the total content of GLUT4 and insulin receptor was not different in myopathic vs. control horses. PSSM therefore represents a novel disorder where enhanced insulin sensitivity and elevated glucose excursion leads to increased synthesis of muscle glycogen, which in our horses appears to be independent of augmented GLUT4 or IR quantity.
Annandale
Erin J
EJ
Department of Clinical and Population Sciences, University of Minnesota, 1365 Gortner Ave., St Paul, MN 55108, USA.
Valberg
Stephanie J
SJ
Mickelson
James R
JR
Seaquist
Elizabeth R
ER
D015061:1,4-alpha-Glucan Branching Enzyme / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D005260:Female; D045268:Flowmeters; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006651:Histocytochemistry / Q000379:methods; D006734:Horse Diseases / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D012206:Rhabdomyolysis / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary; D013997:Time Factors
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011134:Polysaccharides; D019298:Glucose-6-Phosphate; D006003:Glycogen; D015061:1,4-alpha-Glucan Branching Enzyme; D011972:Receptor, Insulin; D005947:Glucose