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Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate
Gyeong Ryul Ryu, Jun Mo Yoo, Esder Lee, Seung-Hyun Ko, Yu-Bae Ahn, Ki-Ho Song
Diabetes Metab J. 2011;35(1):65-71.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.65
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  • 38 Download
  • 4 Crossref
AbstractAbstract PDFPubReader   
Background

Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise mechanism of this adverse effect is not well understood.

Methods

INS-1 rat-derived insulin-secreting cells were exposed to 30 mM glucose and 0.25 mM palmitate for 48 hours.

Results

The production of reactive oxygen species increased significantly. Pancreatic and duodenal homeobox 1 (Pdx1) expression was down-regulated, as assessed by reverse transcription-polymerase chain reaction and Western blot analyses. The promoter activities of insulin and Pdx1 were also diminished. Of note, there was nucleocytoplasmic translocation of Pdx1, which was partially prevented by treatment with an antioxidant, N-acetyl-L-cysteine.

Conclusion

Our data suggest that prolonged exposure of beta cells to elevated levels of glucose and palmitate negatively affects Pdx1 expression via oxidative stress.

Citations

Citations to this article as recorded by  
  • Nrf2 Activation Protects Mouse Beta Cells from Glucolipotoxicity by Restoring Mitochondrial Function and Physiological Redox Balance
    Johanna Schultheis, Dirk Beckmann, Dennis Mulac, Lena Müller, Melanie Esselen, Martina Düfer
    Oxidative Medicine and Cellular Longevity.2019; 2019: 1.     CrossRef
  • Early overnutrition reduces Pdx1 expression and induces β cell failure in Swiss Webster mice
    Maria M. Glavas, Queenie Hui, Eva Tudurí, Suheda Erener, Naomi L. Kasteel, James D. Johnson, Timothy J. Kieffer
    Scientific Reports.2019;[Epub]     CrossRef
  • Anti-diabetic effect of mulberry leaf polysaccharide by inhibiting pancreatic islet cell apoptosis and ameliorating insulin secretory capacity in diabetic rats
    Yao Zhang, Chunjiu Ren, Guobing Lu, Zhimei Mu, Weizheng Cui, Huiju Gao, Yanwen Wang
    International Immunopharmacology.2014; 22(1): 248.     CrossRef
  • The Furan Fatty Acid Metabolite CMPF Is Elevated in Diabetes and Induces β Cell Dysfunction
    Kacey J. Prentice, Lemieux Luu, Emma M. Allister, Ying Liu, Lucy S. Jun, Kyle W. Sloop, Alexandre B. Hardy, Li Wei, Weiping Jia, I. George Fantus, Douglas H. Sweet, Gary Sweeney, Ravi Retnakaran, Feihan F. Dai, Michael B. Wheeler
    Cell Metabolism.2014; 19(4): 653.     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
  • 3,976 View
  • 30 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
  • Correlation between HbA1c and Triglyceride Level with Coronary Stenosis Degree in Type 2 Diabetes Mellitus with Coronary Heart Disease
    Laily Adninta, Indranila Samsuria, Edward Kurnia Setiawan Limijadi
    Open Access Macedonian Journal of Medical Sciences.2022; 10(B): 944.     CrossRef
  • Age‐specific associations of glycated haemoglobin variability with cardiovascular disease and mortality in patients with type 2 diabetes mellitus: A 10‐ year cohort study
    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
  • Resolution on the results of the first working meeting of the scientific advisory board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy»
    Mikhail B. Antsiferov, Gagik R. Galstyan, Alexey V. Zilov, Alexander Y. Mayorov, Tatyana N. Markova, Nikolay A. Demidov, Olga M. Koteshkova, Dmitry N. Laptev, Alisa V. Vitebskaya
    Diabetes mellitus.2019; 22(3): 281.     CrossRef
  • Intermittent High Glucose Enhances the Proliferation of Rat Aortic Vascular Smooth Muscle Cells More Than Constant High Glucose via the Mitogen-Activated Protein Kinase Pathway
    Sung Hoon Yu, Hyung Joon Yoo, Dong Hyun Kang, Shin Je Moon, Jae Myung Yu
    Annals of Geriatric Medicine and Research.2017; 21(3): 131.     CrossRef
  • Association of variability in hemoglobin A1c with cardiovascular diseases and mortality in Chinese patients with type 2 diabetes mellitus — A retrospective population-based cohort study
    Eric Yuk Fai Wan, Colman Siu Cheung Fung, Daniel Yee Tak Fong, Cindy Lo Kuen Lam
    Journal of Diabetes and its Complications.2016; 30(7): 1240.     CrossRef
  • 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
    Ye-Hwang Cheong, Mi-Kyung Kim, Moon-Ho Son, Bong-Kiun Kaang
    Biochemical and Biophysical Research Communications.2011; 414(1): 220.     CrossRef
  • Overexpression of Insig-1 protects β cell against glucolipotoxicity via SREBP-1c
    Ke Chen, ping jin, Hong-hui He, Yan-hong Xie, Xiao-yun Xie, Zhao-hui Mo
    Journal of Biomedical Science.2011;[Epub]     CrossRef
  • Association of glycemic variability and the presence and severity of coronary artery disease in patients with type 2 diabetes
    Gong Su, Shuhua Mi, Hong Tao, Zhao Li, Hongxia Yang, Hong Zheng, Yun Zhou, Changsheng Ma
    Cardiovascular Diabetology.2011;[Epub]     CrossRef
  • Lithospermic acid B protects beta-cells from cytokine-induced apoptosis by alleviating apoptotic pathways and activating anti-apoptotic pathways of Nrf2–HO-1 and Sirt1
    Byung-Wan Lee, Sung Wan Chun, Soo Hyun Kim, Yongho Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee
    Toxicology and Applied Pharmacology.2011; 252(1): 47.     CrossRef
  • WITHDRAWN: Effect of blood glucose fluctuation on the function of rat pancreatic islets in vivo
    Wang Yanjun, Xiao Yue, Li Shixing
    Regulatory Peptides.2011;[Epub]     CrossRef
Taurine-Mediated Restoration of Glucose Sensitivity of Pancreatic Beta Cells in OLETF Rats.
So Yeon Kim, Keun Gyu Park, In Kyu Lee, Seong Il Nam, Dae Kyu Song
Korean Diabetes J. 2005;29(3):198-205.   Published online May 1, 2005
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  • 19 Download
AbstractAbstract PDF
BACKGROUND
An OLETF(Otsuka Long-Evans Tokushima Fatty) rat is a model of type 2 diabetes that is characterized by obesity-induced insulin resistance. Taurine has been known to be beneficial for type 2 diabetes. This study evaluated the potential taurine effect on the insulin response to high glucose in the islets of OLETF rats. METHODS: One percent of taurine was put in the drinking water for the taurine group of OLETF rats at the time of their being 20 to 39 weeks of age. At 40 weeks, the pancreatic islets and beta cells were obtained to measure the glucose-stimulated insulin secretion(GSIS) and the ATP-sensitive K+(KATP) channel current. RESULTS: Taurine supplementation had no effect on the weight change of the rats when this was measured weekly from 20 to 39 weeks(mean+/-SE: 702+/-19g in the control group vs. 688+/-18g in the taurine group at the 39th week). However, the GSIS was significantly potentiated in the taurine-treated rats(8.9+/-1.3% vs. 13.2+/-3.2% of the total secreted at 15 mM glucose for 1h). The glucose-induced KATP channel inhibition in the beta cells was also greater in the taurine group. CONCLUSION: Taurine supplementation is a beneficial tool for the restoration of GSIS in the pancreatic islet of the OLETF rats. Maintenance of blood taurine level may be important in treating type 2 diabetic patients, who are subject to a low blood level of taurine

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