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Suppression of phosphatase and tensin homolog protects insulin-resistant cells from apoptosis

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In the present study, a glucosamine-induced model of insulin-resistant skeletal muscle cells was established in order to investigate the effect of inhibition of phosphatase and tensin homolog (PTEN)/5'-adenosine monophosphate-activated protein kinase (AMPK) on these cells. The glucosamineinduced insulinresistant skeletal muscle cells were produced and the rate of glucose uptake was measured using the glucose oxidaseperoxidase method. The expression levels of PTEN and phosphorylated PTEN (pPTEN) were assessed using western blotting. Glucose transporter 4 (GLUT4) translocation was detected by immunofluorescence. Cell apoptosis was evaluated using flow cytometry. Following insulin stimulation, the rate of glucose uptake was significantly reduced in the cells with glucosamineinduced insulinresistance in comparison with those in the control group. The expression and translocation of GLUT4 were reduced in the insulinresistant muscle cells. By contrast, the expression of PTEN and pPTEN as well as apoptosis were significantly increased. Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulinresistant skeletal muscle cells, there was an increase in the rate of glucose uptake, an increase in GLUT4 expression and its translocation, a reduction in the expression of PTEN and pPTEN, and a decrease in cell apoptosis compared with untreated insulinresistant cells. Glucosamine may be used to produce an effective model of insulinresistant skeletal muscle cells. Cells with glucosamineinduced insulinresistance exhibited a reduced expression of GLUT4 and dysfunction in GLUT4 translocation, as well as increased activation of PTEN and increased cell apoptosis. Inhibition of PTEN or its upstream regulator, AMPK, protects glucosamineinduced insulin-resistant skeletal muscle cells from apoptosis.
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Document Type: Research Article

Affiliations: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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