title: Suppression of phosphatase and tensin homolog protects insulin-resistant cells from apoptosis.
abstract: 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 glucosamine-induced insulin-resistant skeletal muscle cells were produced and the rate of glucose uptake was measured using the glucose oxidase-peroxidase method. The expression levels of PTEN and phosphorylated PTEN (p-PTEN) 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 glucosamine-induced insulin-resistance in comparison with those in the control group. The expression and translocation of GLUT4 were reduced in the insulin-resistant muscle cells. By contrast, the expression of PTEN and p-PTEN as well as apoptosis were significantly increased. Following treatment with bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant 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 p-PTEN, and a decrease in cell apoptosis compared with untreated insulin-resistant cells. Glucosamine may be used to produce an effective model of insulin-resistant skeletal muscle cells. Cells with glucosamine-induced insulin-resistance 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 glucosamine-induced insulin-resistant skeletal muscle cells from apoptosis.
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Di-Fei
authors.initials: DF
authors.lastname: Wang
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Hui-Jing
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Jian-Qiu
authors.initials: JQ
authors.lastname: Gu
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Cao
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005944:Glucosamine; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008687:Metformin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D014638:Vanadates; D008687:Metformin; D051059:PTEN Phosphohydrolase; D005944:Glucosamine