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The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition
- Source :
- Diabetes & Metabolism Journal, Vol 35, Iss 5, Pp 480-488 (2011)
- Publication Year :
- 2011
- Publisher :
- Korean Diabetes Association, 2011.
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Abstract
- Backgroundβ-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.MethodsApoptosis 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.ResultsAddition 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.ConclusionGB 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.
Details
- Language :
- English
- ISSN :
- 22336079 and 22336087
- Volume :
- 35
- Issue :
- 5
- Database :
- Directory of Open Access Journals
- Journal :
- Diabetes & Metabolism Journal
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5003f1b0d14f968a2ba96366980aa4
- Document Type :
- article
- Full Text :
- https://doi.org/10.4093/dmj.2011.35.5.480