In response to insulin, several proteins are phosphorylated on tyrosine and on serine/threonine residues. Decreased phosphorylation of signaling peptides by a defective insulin receptor kinase may be a cause of insulin resistance. Accordingly, inhibition of the appropriate phosphatases might increase the phosphorylation state of these signaling peptides and thereby elicit increased glucose transport. The purpose of this study was to examine the effect of the serine/threonine phosphatase inhibitor okadaic acid and the tyrosine phosphatase inhibitors phenylarsine oxide and vanadate on 2-deoxyglucose transport in insulin-resistant human skeletal muscle. All three phosphatase inhibitors stimulated 2-deoxyglucose transport in insulin-resistant skeletal muscle. These data suggest that these compounds have bypassed a defect in at least one of the signaling pathways leading to glucose transport. Furthermore, maximal transport rates induced by the simultaneous presence of insulin and phosphatase inhibitor in insulin-resistant muscle were equal to insulin-stimulated rates in lean control subjects. However, both vanadate alone and vanadate plus insulin stimulated 2-deoxyglucose transport significantly more in insulin-sensitive tissue than in insulin-resistant tissue. These results demonstrate that although vanadate is able to stimulate glucose transport in insulin-resistant muscle, it is not able to normalize transport to the same rate achieved in insulin-sensitive muscle.
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Original Articles|
June 01 1995
Okadaic Acid, Vanadate, and Phenylarsine Oxide Stimulate 2-Deoxyglucose Transport in Insulin-Resistant Human Skeletal Muscle
Julie O Carey;
Julie O Carey
Departments of Biochemistry and Surgery, East Carolina University, School of Medicine
Greenville, North Carolina
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John L Azevedo, Jr;
John L Azevedo, Jr
Departments of Biochemistry and Surgery, East Carolina University, School of Medicine
Greenville, North Carolina
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Patricia G Morris;
Patricia G Morris
Departments of Biochemistry and Surgery, East Carolina University, School of Medicine
Greenville, North Carolina
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Walter J Pories;
Walter J Pories
Departments of Biochemistry and Surgery, East Carolina University, School of Medicine
Greenville, North Carolina
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G Lynis Dohm
G Lynis Dohm
Departments of Biochemistry and Surgery, East Carolina University, School of Medicine
Greenville, North Carolina
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Address correspondence and reprint requests to Dr. Julie 0. Carey, Department of Medicine, Section of Endocrinology, School of Medicine, East Carolina University, Greenville, NC 27585.
Diabetes 1995;44(6):682–688
Article history
Received:
June 09 1994
Revision Received:
February 01 1995
Accepted:
February 01 1995
PubMed:
7789633
Citation
Julie O Carey, John L Azevedo, Patricia G Morris, Walter J Pories, G Lynis Dohm; Okadaic Acid, Vanadate, and Phenylarsine Oxide Stimulate 2-Deoxyglucose Transport in Insulin-Resistant Human Skeletal Muscle. Diabetes 1 June 1995; 44 (6): 682–688. https://doi.org/10.2337/diab.44.6.682
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