Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Author index

Page Path
HOME > Browse > Author index
Search
Esder Lee  (Lee E) 3 Articles
Basic Research
Hypoxia Increases β-Cell Death by Activating Pancreatic Stellate Cells within the Islet
Jong Jin Kim, Esder Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Ki-Ho Song
Diabetes Metab J. 2020;44(6):919-927.   Published online May 11, 2020
DOI: https://doi.org/10.4093/dmj.2019.0181
  • 5,865 View
  • 145 Download
  • 15 Web of Science
  • 16 Crossref
AbstractAbstract PDFPubReader   ePub   
Background

Hypoxia can occur in pancreatic islets in type 2 diabetes mellitus. Pancreatic stellate cells (PSCs) are activated during hypoxia. Here we aimed to investigate whether PSCs within the islet are also activated in hypoxia, causing β-cell injury.

Methods

Islet and primary PSCs were isolated from Sprague Dawley rats, and cultured in normoxia (21% O2) or hypoxia (1% O2). The expression of α-smooth muscle actin (α-SMA), as measured by immunostaining and Western blotting, was used as a marker of PSC activation. Conditioned media (hypoxia-CM) were obtained from PSCs cultured in hypoxia.

Results

Islets and PSCs cultured in hypoxia exhibited higher expressions of α-SMA than did those cultured in normoxia. Hypoxia increased the production of reactive oxygen species. The addition of N-acetyl-L-cysteine, an antioxidant, attenuated the hypoxia-induced PSC activation in islets and PSCs. Islets cultured in hypoxia-CM showed a decrease in cell viability and an increase in apoptosis.

Conclusion

PSCs within the islet are activated in hypoxia through oxidative stress and promote islet cell death, suggesting that hypoxia-induced PSC activation may contribute to β-cell loss in type 2 diabetes mellitus.

Citations

Citations to this article as recorded by  
  • Effects of hypoxia in the diabetic corneal stroma microenvironment
    Purnima Sharma, Jian-Xing Ma, Dimitrios Karamichos
    Experimental Eye Research.2024; 240: 109790.     CrossRef
  • Visualizing hypoxic modulation of beta cell secretions via a sensor augmented oxygen gradient
    Kai Duan, Mengyang Zhou, Yong Wang, Jose Oberholzer, Joe F. Lo
    Microsystems & Nanoengineering.2023;[Epub]     CrossRef
  • Pancreatic stellate cells promote pancreatic β-cell death through exosomal microRNA transfer in hypoxia
    Esder Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Ki-Ho Song
    Molecular and Cellular Endocrinology.2023; 572: 111947.     CrossRef
  • Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy
    Zhengfeng Wang, Ru He, Shi Dong, Wence Zhou
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Recent advances in the development of bioartificial pancreas using 3D bioprinting for the treatment of type 1 diabetes: a review
    Anushikha Ghosh, Arka Sanyal, Abhik Mallick
    Exploration of Medicine.2023; : 886.     CrossRef
  • Pancreas and islet morphology in cystic fibrosis: clues to the etiology of cystic fibrosis-related diabetes
    Sarah S. Malik, Diksha Padmanabhan, Rebecca L. Hull-Meichle
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Diabetic mellitus, vascular calcification and hypoxia: A complex and neglected tripartite relationship
    Xue-Jiao Sun, Nai-Feng Liu
    Cellular Signalling.2022; 91: 110219.     CrossRef
  • HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer
    Shin Hamada, Ryotaro Matsumoto, Atsushi Masamune
    Cancers.2022; 14(2): 411.     CrossRef
  • Pancreatic Stellate Cells and Metabolic Alteration: Physiology and Pathophysiology
    Shin Hamada, Ryotaro Matsumoto, Atsushi Masamune
    Frontiers in Physiology.2022;[Epub]     CrossRef
  • Exosomal miR-140–3p and miR-143–3p from TGF-β1-treated pancreatic stellate cells target BCL2 mRNA to increase β-cell apoptosis
    Xiangyun Zhu, Dechen Liu, Guoqing Li, Mengmeng Zhi, Ji Sun, Liang Qi, Jingbo Li, Stephen J. Pandol, Ling Li
    Molecular and Cellular Endocrinology.2022; 551: 111653.     CrossRef
  • Mitochondria oxidative stress mediated nicotine-promoted activation of pancreatic stellate cells by regulating mitochondrial dynamics
    Yue Yuan, Zhiren Li, Miaomiao Li, Tong Jin, Xiaoyun Zhang, Xinjuan Liu, Jianyu Hao
    Toxicology in Vitro.2022; 84: 105436.     CrossRef
  • Antioxidant Mitoquinone Alleviates Chronic Pancreatitis via Anti-Fibrotic and Antioxidant Effects
    Miaomiao Li, Yue Yuan, Xue Han, Xinjuan Liu, Weizhen Zhang, Jianyu Hao
    Journal of Inflammation Research.2022; Volume 15: 4409.     CrossRef
  • Diabetic Ferroptosis and Pancreatic Cancer: Foe or Friend?
    Le Li, Xing-jia Yu, Lei Gao, Long Cheng, Bei Sun, Gang Wang
    Antioxidants & Redox Signaling.2022; 37(16-18): 1206.     CrossRef
  • Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia
    Matias Estaras, Manuel R. Gonzalez-Portillo, Miguel Fernandez-Bermejo, Jose M. Mateos, Daniel Vara, Gerardo Blanco-Fernandez, Diego Lopez-Guerra, Vicente Roncero, Gines M. Salido, Antonio González
    International Journal of Molecular Sciences.2021; 22(11): 5555.     CrossRef
  • Integrated pancreatic microcirculatory profiles of streptozotocin‐induced and insulin‐administrated type 1 diabetes mellitus
    Yuan Li, Bingwei Li, Bing Wang, Mingming Liu, Xiaoyan Zhang, Ailing Li, Jian Zhang, Honggang Zhang, Ruijuan Xiu
    Microcirculation.2021;[Epub]     CrossRef
  • Pancreatic stellate cells - rising stars in pancreatic pathologies
    P Hrabák, M Kalousová, T Krechler, T Zima
    Physiological Research.2021; (S4): S597.     CrossRef
Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury
Eun-Mi Lee, Young-Eun Lee, Esder Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Sung-Dae Moon, Ki-Ho Song, Yu-Bae Ahn
Diabetes Metab J. 2011;35(5):469-479.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.469
  • 3,564 View
  • 35 Download
  • 19 Crossref
AbstractAbstract PDFPubReader   
Background

Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.

Methods

Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.

Results

CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.

Conclusion

Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.

Citations

Citations to this article as recorded by  
  • Diabetes: Risk factor and translational therapeutic implications for Alzheimer's disease
    Jeffrey Cummings, Andrew Ortiz, Janelle Castellino, Jefferson Kinney
    European Journal of Neuroscience.2022; 56(9): 5727.     CrossRef
  • The ischaemic preconditioning paradox and its implications for islet isolation from heart-beating and non heart-beating donors
    Daniel Brandhorst, Heide Brandhorst, Samuel Acreman, Paul R. V. Johnson
    Scientific Reports.2022;[Epub]     CrossRef
  • CYTOCHROMES OF MITOCHONDRIES AND ACTIVITY OF HEME METABOLISM ENZYMES IN THE LIVER UNDER DIFFERENT NUTRIENT REGIMES
    G.P. Kopylchuk, Z.-M. I. Grynenkiv, O.M. Voloshchuk
    Fiziolohichnyĭ zhurnal.2021; 67(2): 37.     CrossRef
  • Heme Oxygenase-1 (HMOX-1) and inhibitor of differentiation proteins (ID1, ID3) are key response mechanisms against iron-overload in pancreatic β-cells
    Mawieh Hamad, Abdul Khader Mohammed, Mahmood Y. Hachim, Debasmita Mukhopadhy, Anila Khalique, Amina Laham, Sarah Dhaiban, Khuloud Bajbouj, Jalal Taneera
    Molecular and Cellular Endocrinology.2021; 538: 111462.     CrossRef
  • Food-derived cyanidin-3-O-glucoside alleviates oxidative stress: evidence from the islet cell line and diabetic db/db mice
    Xiang Ye, Wen Chen, Pengcheng Tu, Ruoyi Jia, Yangyang Liu, Yonglu Li, Qiong Tang, Xiaodong Zheng, Qiang Chu
    Food & Function.2021; 12(22): 11599.     CrossRef
  • Telmisartan protects against high glucose/high lipid‐induced apoptosis and insulin secretion by reducing the oxidative and ER stress
    Yan Wang, Jingjing Xue, Yan Li, Xin Zhou, Shun Qiao, Dewu Han
    Cell Biochemistry and Function.2019; 37(3): 161.     CrossRef
  • Ropivacaine regulates the expression and function of heme oxygenase-1
    Xiangbiao Yan, Yu Li, Xuechang Han, Xu Dong, Yajie Zhang, Qunzhi Xing
    Biomedicine & Pharmacotherapy.2018; 103: 284.     CrossRef
  • A review on heme oxygenase-1 induction: is it a necessary evil
    Ajaz Ahmad Waza, Zeenat Hamid, Sajad Ali, Shabir Ahmad Bhat, Musadiq Ahmad Bhat
    Inflammation Research.2018; 67(7): 579.     CrossRef
  • Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects
    Hee Jae Lee, Hye In Seo, Hee Yun Cha, Yun Jung Yang, Soo Hyun Kwon, Soo Jin Yang
    Clinical Nutrition Research.2018; 7(4): 229.     CrossRef
  • Social, economic, and policy implications of organ preservation advances
    Alyssa Ward, David K. Klassen, Kate M. Franz, Sebastian Giwa, Jedediah K. Lewis
    Current Opinion in Organ Transplantation.2018; 23(3): 336.     CrossRef
  • Geniposide protects pancreatic β cells from high glucose‐mediated injury by activation of AMP‐activated protein kinase
    Chunyan Liu, Yanan Hao, Fei Yin, Yonglan Zhang, Jianhui Liu
    Cell Biology International.2017; 41(5): 544.     CrossRef
  • Eff ects of hemin, a heme oxygenase-1 inducer in L-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats
    N. M. Aziz, M. Y. Kamel, R. A. Rifaai
    Endocrine Regulations.2017; 51(1): 20.     CrossRef
  • Downregulation of microRNA-155 ameliorates high glucose-induced endothelial injury by inhibiting NF-κB activation and promoting HO-1 and NO production
    Xi Zhang, Xiangyang Liu, Yang Li, Jingbo Lai, Nana Zhang, Jie Ming, Xianjie Ma, Qiuhe Ji, Ying Xing
    Biomedicine & Pharmacotherapy.2017; 88: 1227.     CrossRef
  • Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreaticβ-Cells Function
    Catalina Carrasco-Pozo, Kah Ni Tan, Martin Gotteland, Karin Borges
    Oxidative Medicine and Cellular Longevity.2017; 2017: 1.     CrossRef
  • Aromatic malononitriles stimulate the resistance of insulin-producing beta-cells to oxidants and inflammatory cytokines
    Kyril Turpaev, Nils Welsh
    European Journal of Pharmacology.2016; 784: 69.     CrossRef
  • Differences in insulin biosynthesis pathway between small and large islets do not correspond to insulin secretion
    Han-Hung Huang, Lisa Stehno-Bittel
    Islets.2015; 7(5): e1129097.     CrossRef
  • A newly identified polysaccharide from Ganoderma atrum attenuates hyperglycemia and hyperlipidemia
    Kexue Zhu, Shaoping Nie, Chuan Li, Suli Lin, Mengmeng Xing, Wenjuan Li, Deming Gong, Mingyong Xie
    International Journal of Biological Macromolecules.2013; 57: 142.     CrossRef
  • Glycated Albumin Causes Pancreatic β-Cells Dysfunction Through Autophagy Dysfunction
    Young Mi Song, Sun Ok Song, Young-Hye You, Kun-Ho Yoon, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee, Ji-Won Kim, Byung-Wan Lee
    Endocrinology.2013; 154(8): 2626.     CrossRef
  • Chronic Resveratrol Treatment Protects Pancreatic Islets against Oxidative Stress in db/db Mice
    Young-Eun Lee, Ji-Won Kim, Eun-Mi Lee, Yu-Bae Ahn, Ki-Ho Song, Kun-Ho Yoon, Hyung-Wook Kim, Cheol-Whee Park, Guolian Li, Zhenqi Liu, Seung-Hyun Ko, Kathrin Maedler
    PLoS ONE.2012; 7(11): e50412.     CrossRef
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
  • 2,981 View
  • 36 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

Diabetes Metab J : Diabetes & Metabolism Journal