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KMID : 1200020110350050480
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Diabetes & Metabolism Journal
2011 Volume.35 No. 5 p.480 ~ p.488
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The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition
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Kwon Min-Jeong
Ko Jung-Hae
Jun Hae-Jung
Kim Tae-Kyun
Lee Soon-Hee
Ko Kyung-Soo
Rhee Byoung-Doo
Park Jeong-Hyun
Chung Hye-Suk
Yoon Chang-Shin
Kim Mi-Kyung
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Abstract
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Background:β-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.
Methods:Apoptosis was induced by adding various concentrations of GB (0.001 to 200 μM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.
Results:Addition of any concentration of GB in 150 μM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.
Conclusion:GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load.
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KEYWORD
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Apoptosis, Endoplasmic reticulum stress, Glyburide, Insulin-secreting cells
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