Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Search

Page Path
HOME > Search
4 "Young Yun Jang"
Filter
Filter
Article category
Keywords
Publication year
Authors
Original Articles
The Effect of Tribbles-Related Protein 3 on ER Stress-Suppressed Insulin Gene Expression in INS-1 Cells
Young Yun Jang, Nam Keong Kim, Mi Kyung Kim, Ho Young Lee, Sang Jin Kim, Hye Soon Kim, Hye-Young Seo, In Kyu Lee, Keun Gyu Park
Korean Diabetes J. 2010;34(5):312-319.   Published online October 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.5.312
  • 3,657 View
  • 32 Download
  • 5 Crossref
AbstractAbstract PDFPubReader   
Background

The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression.

Methods

The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter.

Results

The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression.

Conclusions

This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.

Citations

Citations to this article as recorded by  
  • Endoplasmic reticulum stress causes insulin resistance by inhibiting delivery of newly synthesized insulin receptors to the cell surface
    Max Brown, Samantha Dainty, Natalie Strudwick, Adina D. Mihai, Jamie N. Watson, Robina Dendooven, Adrienne W. Paton, James C. Paton, Martin Schröder, James Arthur Olzmann
    Molecular Biology of the Cell.2020; 31(23): 2597.     CrossRef
  • PTB and TIAR binding to insulin mRNA 3′- and 5′UTRs; implications for insulin biosynthesis and messenger stability
    Rikard G. Fred, Syrina Mehrabi, Christopher M. Adams, Nils Welsh
    Heliyon.2016; 2(9): e00159.     CrossRef
  • Asna1/TRC40 Controls β-Cell Function and Endoplasmic Reticulum Homeostasis by Ensuring Retrograde Transport
    Stefan Norlin, Vishal S. Parekh, Peter Naredi, Helena Edlund
    Diabetes.2016; 65(1): 110.     CrossRef
  • Role of the Unfolded Protein Response inβCell Compensation and Failure during Diabetes
    Nabil Rabhi, Elisabet Salas, Philippe Froguel, Jean-Sébastien Annicotte
    Journal of Diabetes Research.2014; 2014: 1.     CrossRef
  • Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review
    Mi-Kyung Kim, Hye-Soon Kim, In-Kyu Lee, Keun-Gyu Park
    Experimental Diabetes Research.2012; 2012: 1.     CrossRef
The Effect of Chronic High Glucose Concentration on Endoplasmic Reticulum Stress in INS-1 Cells.
Mi Kyung Kim, Hye Young Seo, Tae Sung Yun, Nam Kyung Kim, Yu Jin Hah, Yun Jung Kim, Ho Chan Cho, Young Yun Jang, Hye Soon Kim, Seong Yeol Ryu, In Kyu Lee, Keun Gyu Park
Korean Diabetes J. 2008;32(2):112-120.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.112
  • 2,803 View
  • 31 Download
AbstractAbstract PDF
BACKGROUND
The highly developed endoplasmic reticulum (ER) structure is one of the characteristic features of pancreatic beta-cells. Recent study showed that ER stress causes beta-cell dysfunction. However, little is known about the effects of high glucose concentration on induction of ER stress in pancreatic beta-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 eIF2alpha 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 eIF2alpha, 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 beta-cell dysfunction are needed.
Ascochlorin Derivative, AS-6, Inhibits TNF-alpha-Induced fractalkine, MCP-1 and VCAM-1 Expression in Rat Aortic Smooth Muscle Cells.
Young Yun Jang, Sang Yoon Kim, Nam Keong Kim, Mi Kyung Kim, Hee Kyoung Kim, Hye Soon Kim, Chang Wook Nam, Seong Yeol Ryu, Sung Il Nam, Keun Gyu Park
Korean Diabetes J. 2005;29(5):401-408.   Published online September 1, 2005
  • 976 View
  • 17 Download
AbstractAbstract PDF
BACKGOUND: Inflammation is one of the key mechanisms in the development and progression of atherosclerosis. Accumulating evidence suggests that peroxisome proliferators- activated receptorgamma(PPARgamma) plays an important role in the prevention of arterial inflammation and the formation of atherogenesis. This study was designed to evaluate whether the new synthetic PPARgamma, ascochlorin-6(AS-6) has anti-inflammatory and anti-atherogenic effects in primary cultured rat vascular smooth muscle cells(VSMCs). METHODS: Rat VSMCs were isolated and cultured. Northern and Western blot analyses were performed to evaluate the effects of AS-6 on the expressions of tumor necrosis factor (TNF)-alpha-stimulated fractalkine, monocyte chemoattractant protein(MCP)-1 and vascular cell adhesion molecule (VCAM)-1 in VSMCs. A gel shift assay was performed to examine the mechanism by which AS-6 inhibits the expressions of fractalkine, MCP-1 and VCAM-1. RESULTS: TNF-alpha markedly induced the expressions of fractalkine, MCP-1 and VCAM-1 in primary cultured VSMCs. AS-6 inhibited the expressions of TNF-alpha-stimulated fractalkine, MCP-1 and VCAM-1 in primary cultured VSMCs. The result of the gel shift assay suggested the inhibitory effects of AS-6 on the expressions of TNF-alpha-stimulated fractalkine, MCP-1 and VCAM-1 were mediated through a nuclear factor kappaB associated pathway. CONCLUSION: The present study shows that AS-6 has anti-inflammatory effects on VSMCs, suggesting the possibility for the use of AS-6 for prevention of the development and progression of atherosclerosis.
Comparison of the Relationship of Leptin to Metabolic Parameters Between Premenopausal Normal Weight and Obese Women.
Hee Kyoung Kim, Keun Gyu Park, Mi Kyung Kim, Young Yun Jang, Sang Yoon Kim, Eui Dal Jung, Hye Soo Kim, Ju Ho Do, In Kyu Lee
Korean Diabetes J. 2005;29(3):223-230.   Published online May 1, 2005
  • 957 View
  • 17 Download
AbstractAbstract PDF
BACKGROUND
Leptin is mainly secreted from adipose tissue, and it is a crucial factor for metabolic syndrome that is characterized by obesity, insulin resistance, hypertension and dyslipidemia. We measured the serum leptin concentrations and compared them with the body fat distribution and metabolic risk factors in premenopausal normal weight and obese women. METHODS: 231 premenopausal obese women participated in this study. The subjects were grouped based on their body mass index(BMI). The number of normal weight group women(BMI<25kg/m2) and the number of obese group women(BMI> or = 25kg/m2) were 90 and 141, respectively. We measured the plasma leptin concentration and such metabolic risk factors as fasting glucose, insulin, triglyceride(TG), systolic blood pressure(SBP) and diastolic blood pressure(DBP). The subcutaneous adipose tissue area(SAT) and the visceral adipose tissue area(VAT) were determined by computed tomography. The BMI, waist to hip ratio(WHR) and homeostasis model assessment(HOMA-IR) were calculated. RESULTS: In the obese group, the leptin levels were positively correlated with the BMI and SAT as well as with such metabolic risk factors as fasting serum glucose, insulin, HOMA-IR, TG, SBP and DBP. Although leptin levels were positively correlated with BMI and SAT in the normal weight group, they were not correlated with the metabolic risk factors. CONCLUSION: The present study showed that the leptin levels in the normal weight group were not associated with the metabolic risk factors. Therefore, the degree of obesity must be considered before leptin can be used as a predictor for metabolic syndrome including diabetes and coronary heart disease

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer