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

Wang,Di‑Fei; Yang,Hui‑Jing; Gu,Jian‑Qiu; Cao,Yan‑Li; Meng,Xin; Wang,Xiao‑Li; Lin,Yi‑Chen; Gao,Ming

doi:10.3892/mmr.2015.3771

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

Authors:
- Di‑Fei Wang
- Hui‑Jing Yang
- Jian‑Qiu Gu
- Yan‑Li Cao
- Xin Meng
- Xiao‑Li Wang
- Yi‑Chen Lin
- Ming Gao
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Affiliations: Department of Geriatric Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: May 12, 2015 https://doi.org/10.3892/mmr.2015.3771
Pages: 2695-2700

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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.

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