The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition.
10.4093/dmj.2011.35.5.480
- Author:
Min Jeong KWON
1
;
Hye Suk CHUNG
;
Chang Shin YOON
;
Jung Hae KO
;
Hae Jung JUN
;
Tae Kyun KIM
;
Soon Hee LEE
;
Kyung Soo KO
;
Byoung Doo RHEE
;
Mi Kyung KIM
;
Jeong Hyun PARK
Author Information
1. Paik Diabetes Center, Department of Internal Medicine, Inje University College of Medicine, Busan, Korea. pjhdoc@chol.com
- Publication Type:Original Article
- Keywords:
Apoptosis;
Endoplasmic reticulum stress;
Glyburide;
Insulin-secreting cells
- MeSH:
Annexin A5;
Apoptosis;
Blotting, Western;
Caspase 3;
Endoplasmic Reticulum;
Endoplasmic Reticulum Stress;
Eukaryotic Initiation Factor-2;
Glucose;
Glyburide;
Hypoglycemic Agents;
Insulin-Secreting Cells;
Peptide Initiation Factors;
Phosphatidylinositol 3-Kinase;
Phosphorylation;
Transcription Factors
- From:Diabetes & Metabolism Journal
2011;35(5):480-488
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: beta-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 beta-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 microM) 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 microM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2alpha) 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-2alpha may attenuate ER stress for adaptation to increased ER protein load.
