KMID : 1199120080320020112
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Korean Diabetes Journal 2008 Volume.32 No. 2 p.112 ~ p.120
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The Effect of Chronic High Glucose Concentration on Endoplasmic Reticulum Stress in INS-1 Cells
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Kim Mi-Kyung
Seo Hye-Young Yun Tae-Seung Kim Nam-Keong Hah Yu-Jin Kim Yun-Jung Cho Ho-Chan Jang Young-Yun Kim Hye-Sun Ryu Seong-Yeol Lee In-Kyu Park Keun-Gyu
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Abstract
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Background: The highly developed endoplasmic reticulum (ER) structure is one of the characteristic features of pancreatic ¥â-cells. Recent study showed that ER stress causes ¥â-cell dysfunction. However, little is known about the effects of high glucose concentration on induction of ER stress in pancreatic ¥â-cells. Therefore, this study was designed to evaluate whether exposure of high glucose concentration in rat insulinoma cell line, INS-1 cell induces ER stress and whether ER stress decreases insulin gene expression.
Methods: The effect of 30 mM glucose on insulin expression and secretion in INS-1 cells was evaluated by Northern blot analysis and glucose-stimulated insulin secretion (GSIS). Cell viability was evaluated by XTT assay. The effect of 30 mM glucose on phosphorylation of eIF2¥á and CHOP expression, which are markers of ER stress were evaluated by Western blot analysis. RT-PCR analysis was performed to determine whether high glucose concentration induces XBP-1 splicing. To investigate whether ER stress decreases insulin gene expression, the effect of tunicamycin on insulin mRNA expression was evaluated by Northern blot analysis.
Results: The prolonged exposure of INS-1 cells with the 30 mM glucose concentration decreased insulin mRNA expression in a time dependent manner and impaired GSIS while did not influence on cell viability. 30 mM glucose increased phosphorylation of eIF2¥á, XBP-1 splicing and CHOP expression in INS-1 cells. Tunicamycin-treated INS-1 increased XBP-1 splicing and decreased insulin mRNA expression in a dose dependent manner.
Conclusion: This study showed that prolonged exposure of INS-1 with high glucose concentration induces ER stress and ER stress decreases insulin gene expression. Further studies about underlying molecular mechanism by which ER stress induces ¥â-cell dysfunction are needed. (KOREAN DIABETES J 32:112~120, 2008)
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KEYWORD
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Diabetes, Endoplasmicreticulumstress, Hyperglycemia, INS-1 cell, Insulin
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