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Hae Jung Jun  (Jun HJ) 2 Articles
The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition
Min Jeong Kwon, 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
Diabetes Metab J. 2011;35(5):480-488.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.480
  • 4,306 View
  • 58 Download
  • 6 Crossref
AbstractAbstract PDFPubReader   
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.

Citations

Citations to this article as recorded by  
  • The antagonistic atorvastatin-glibenclamide interactions suppressed the atorvastatin-induced Bax/cytochrome c/p53 mRNA expressions and increased Rho A mRNA expression in B16f10 melanoma cell culture
    Maryam Malek, Nasim Dana, Ahmad Ghasemi, Maedeh Ghasemi
    Gene Reports.2021; 23: 101156.     CrossRef
  • Expression profiles of stress-related genes in islets from donors with progressively impaired glucose metabolism
    Marcus Lundberg, Anton Stenwall, Angie Tegehall, Olle Korsgren, Oskar Skog
    Islets.2018; 10(2): 69.     CrossRef
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    Tae Jung, Kyung Choi
    International Journal of Molecular Sciences.2016; 17(2): 192.     CrossRef
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    Carlos Manlio Diaz-Garcia
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  • Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction
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    Autophagy.2012; 8(7): 1085.     CrossRef
  • The Duration of Sulfonylurea Treatment Is Associated withβ-Cell Dysfunction in Patients with Type 2 Diabetes Mellitus
    Mi-Seon Shin, Jee Hee Yu, Chang Hee Jung, Jenie Yoonoo Hwang, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park
    Diabetes Technology & Therapeutics.2012; 14(11): 1033.     CrossRef
The Effect of Glucose Fluctuation on Apoptosis and Function of INS-1 Pancreatic Beta Cells
Mi Kyung Kim, Hye Sook Jung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Tae Kyun Kim, Min Jeong Kwon, Soon Hee Lee, Kyung Soo Ko, Byoung Doo Rhee, Jeong Hyun Park
Korean Diabetes J. 2010;34(1):47-54.   Published online February 28, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.1.47
  • 4,300 View
  • 33 Download
  • 18 Crossref
AbstractAbstract PDFPubReader   
Background

Blood glucose level continuously fluctuates within a certain range in the human body. In diabetes patients, the extent of such fluctuation is large, despite the strict control of blood glucose. Blood glucose fluctuation has been shown to mediate more adverse effects on vascular endothelial cells and diabetes complications than chronic hyperglycemia, which has been explained as due to oxidative stress. As few previous studies have reported the effects of chronic and intermittent hyperglycemia on the apoptosis and function of pancreatic beta cells, this study reported herein was performed to investigate such effects on these cells.

Methods

For chronic hyperglycemia, INS-1 cells were cultured for 5 days with changes of RPMI 1640 medium containing 33 mM glucose every 12 hours. For intermittent hyperglycemia, the medium containing 11 mM glucose was exchanged with the medium containing 33 mM glucose every 12 hours. Apoptosis was assessed by TUNEL assay Hoechst staining and cleaved caspase 3. Insulin secretory capacity was assessed, and the expression of Mn-SOD and Bcl-2 was measured by Western blotting.

Results

In comparison to the control group, INS-1 cells exposed to chronic hyperglycemia and intermittent hyperglycemia showed an increase in apoptosis. The apoptosis of INS-1 cells exposed to intermittent hyperglycemia increased significantly more than the apoptosis of INS-1 cells exposed to chronic hyperglycemia. In comparison to the control group, the insulin secretory capacity in the two hyperglycemic states was decreased, and more with intermittent hyperglycemia than with chronic hyperglycemia. The expression of Mn-SOD and Bcl-2 increased more with chronic hyperglycemia than with intermittent hyperglycemia.

Conclusion

Intermittent hyperglycemia induced a higher degree of apoptosis and decreased the insulin secretory capacity more in pancreatic beta cells than chronic hyperglycemia. This activity may be mediated by the anti-oxidative enzyme Mn-SOD and the anti-apoptotic signal Bcl-2.

Citations

Citations to this article as recorded by  
  • Association between hemoglobin glycation index and diabetic kidney disease in type 2 diabetes mellitus in China: A cross- sectional inpatient study
    Sixu Xin, Xin Zhao, Jiaxiang Ding, Xiaomei Zhang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Plant polyphenols mechanisms of action on insulin resistance and against the loss of pancreatic beta cells
    Camelia Papuc, Gheorghe V. Goran, Corina N. Predescu, Liliana Tudoreanu, Georgeta Ștefan
    Critical Reviews in Food Science and Nutrition.2022; 62(2): 325.     CrossRef
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    Laily Adninta, Indranila Samsuria, Edward Kurnia Setiawan Limijadi
    Open Access Macedonian Journal of Medical Sciences.2022; 10(B): 944.     CrossRef
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    Eric Yuk Fai Wan, Esther Yee Tak Yu, Weng Yee Chin, Florence Ting Yan Ng, Shu Ming Cheryl Chia, Ian Chi Kei Wong, Esther Wai Yin Chan, Cindy Lo Kuen Lam
    Diabetes, Obesity and Metabolism.2020; 22(8): 1316.     CrossRef
  • Molecular Mechanisms of Glucose Fluctuations on Diabetic Complications
    Zhen-Ye Zhang, Ling-Feng Miao, Ling-Ling Qian, Ning Wang, Miao-Miao Qi, Yu-Min Zhang, Shi-Peng Dang, Ying Wu, Ru-Xing Wang
    Frontiers in Endocrinology.2019;[Epub]     CrossRef
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    Annals of Geriatric Medicine and Research.2017; 21(3): 131.     CrossRef
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  • Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress
    You Jeong Kim, Su Min Park, Hye Sook Jung, Eun Ju Lee, Tae Kyoon Kim, Tae-Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Byoung Doo Rhee, Mi-kyung Kim, Jeong Hyun Park
    Islets.2016; 8(3): 57.     CrossRef
  • Different antihyperglycaemic drug effects on glycaemic variability in Type 2 diabetic patients
    Alina Babenko, Elena Ivanovna Krasilnikova, Nikolay Pavlovich Likhonosov, Anna Pavlovna Likhonosova, Elena Nikolaevna Grineva
    Diabetes mellitus.2014; 17(4): 72.     CrossRef
  • Exercising for Metabolic Control: Is Timing Important
    Jonida Haxhi, Alessandro Scotto di Palumbo, Massimo Sacchetti
    Annals of Nutrition and Metabolism.2013; 62(1): 14.     CrossRef
  • Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats
    Yunli Yu, Xinting Wang, Can Liu, Dan Yao, Mengyue Hu, Jia Li, Nan Hu, Li Liu, Xiaodong Liu
    Toxicology and Applied Pharmacology.2013; 266(3): 375.     CrossRef
  • Blood glucose fluctuation affects skin collagen metabolism in the diabetic mouse by inhibiting the mitogen-activated protein kinase and Smad pathways
    X. Ye, X. Cheng, L. Liu, D. Zhao, Y. Dang
    Clinical and Experimental Dermatology.2013; 38(5): 530.     CrossRef
  • Glucose exposure pattern determines glucagon-like peptide 1 receptor expression and signaling through endoplasmic reticulum stress in rat insulinoma cells
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    Biochemical and Biophysical Research Communications.2011; 414(1): 220.     CrossRef
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    Ke Chen, ping jin, Hong-hui He, Yan-hong Xie, Xiao-yun Xie, Zhao-hui Mo
    Journal of Biomedical Science.2011;[Epub]     CrossRef
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