- Islet Studies and Transplantation
-
- Myricetin Protects Against High Glucose-Induced β-Cell Apoptosis by Attenuating Endoplasmic Reticulum Stress via Inactivation of Cyclin-Dependent Kinase 5
-
Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Jae-Han Jeon, Nam Doo Kim, Keun-Gyu Park, Kyu Chang Won, Jaechan Leem, In-Kyu Lee
-
Diabetes Metab J. 2019;43(2):192-205. Published online January 16, 2019
-
DOI: https://doi.org/10.4093/dmj.2018.0052
-
-
5,926
View
-
115
Download
-
37
Web of Science
-
39
Crossref
-
Abstract
PDFSupplementary MaterialPubReader
- Background
Chronic hyperglycemia has deleterious effects on pancreatic β-cell function and turnover. Recent studies support the view that cyclin-dependent kinase 5 (CDK5) plays a role in β-cell failure under hyperglycemic conditions. However, little is known about how CDK5 impair β-cell function. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. In this study, we examined the effect of myricetin on high glucose (HG)-induced β-cell apoptosis and explored the relationship between myricetin and CDK5. MethodsTo address this question, we subjected INS-1 cells and isolated rat islets to HG conditions (30 mM) in the presence or absence of myricetin. Docking studies were conducted to validate the interaction between myricetin and CDK5. Gene expression and protein levels of endoplasmic reticulum (ER) stress markers were measured by real-time reverse transcription polymerase chain reaction and Western blot analysis. ResultsActivation of CDK5 in response to HG coupled with the induction of ER stress via the down regulation of sarcoendoplasmic reticulum calcium ATPase 2b (SERCA2b) gene expression and reduced the nuclear accumulation of pancreatic duodenal homeobox 1 (PDX1) leads to β-cell apoptosis. Docking study predicts that myricetin inhibit CDK5 activation by direct binding in the ATP-binding pocket. Myricetin counteracted the decrease in the levels of PDX1 and SERCA2b by HG. Moreover, myricetin attenuated HG-induced apoptosis in INS-1 cells and rat islets and reduce the mitochondrial dysfunction by decreasing reactive oxygen species production and mitochondrial membrane potential (Δψm) loss. ConclusionMyricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.
-
Citations
Citations to this article as recorded by
- Profiling of secondary metabolite and evaluation of anti-diabetic potency of Crotalaria quinquefolia (L): In-vitro, in-vivo, and in-silico approaches
Nazmun Nahar, Md. Nazmul Hasan Zilani, Partha Biswas, Md. Morsaline Billah, Shabana Bibi, Norah A. Albekairi, Abdulrahman Alshammari, Md. Nazmul Hasan Saudi Pharmaceutical Journal.2024; 32(1): 101887. CrossRef - Mitochondrial aldehyde dehydrogenase-2 coordinates the hydrogen sulfide - AMPK axis to attenuate high glucose-induced pancreatic β-cell dysfunction by glutathione antioxidant system
Udayakumar Karunakaran, Suma Elumalai, Seung Min Chung, Kathrin Maedler, Kyu Chang Won, Jun Sung Moon Redox Biology.2024; 69: 102994. CrossRef - Network-based identification and mechanism exploration of active ingredients against Alzheimer’s disease via targeting endoplasmic reticulum stress from traditional chinese medicine
Zhao Dai, Tian Hu, Junwen Wei, Xue Wang, Chuipu Cai, Yong Gu, Yunhui Hu, Wenjia Wang, Qihui Wu, Jiansong Fang Computational and Structural Biotechnology Journal.2024; 23: 506. CrossRef - Myricetin as a Promising Flavonoid with Multitargeted Biological Activity
A.S. Chiriapkin Juvenis Scientia.2024; 10(1): 5. CrossRef - Naturally occurring small molecules with dual effect upon inflammatory signaling pathways and endoplasmic reticulum stress response
Daniela Correia da Silva, Patrícia Valentão, David M. Pereira Journal of Physiology and Biochemistry.2024; 80(2): 421. CrossRef - Immunopeptidome mining reveals a novel ERS-induced target in T1D
Lina Wang, Shushu Yang, Gaohui Zhu, Jie Li, Gang Meng, Xiaoling Chen, Mengjun Zhang, Shufeng Wang, Xiangqian Li, Yu Pan, Yi Huang, Li Wang, Yuzhang Wu Cellular & Molecular Immunology.2024; 21(6): 604. CrossRef - مقارنة تأثير المستخلص المائي لثمار نبات البامية Abelmoschus Esculentus مع عقار الميتفورمين على إناث الجرذان المصابة بالسكري
عائشة أدريس, إبراهيم عزاقة, فاطمة عبدالله Journal of Pure & Applied Sciences.2024; 23(1): 96. CrossRef - Endoplasmic reticulum stress in pancreatic β-cell dysfunction: The potential therapeutic role of dietary flavonoids
Kingsley C. Mbara, Marthe C.D. Fotsing, Derek T. Ndinteh, Claudine N. Mbeb, Chinekwu S. Nwagwu, Rene Khan, Kopang C. Mokhetho, Himansu Baijnath, Manimbulu Nlooto, Shoeshoe Mokhele, Carmen M. Leonard, Vuyelwa J. Tembu, Clemence Tarirai Current Research in Pharmacology and Drug Discovery.2024; 6: 100184. CrossRef - Myricetin Restores Autophagy to Attenuate Lumbar Intervertebral Disk Degeneration Via Negative Regulation of the JAK2/STAT3 Pathway
Tian Mao, Junchi Fan Biochemical Genetics.2024;[Epub] CrossRef - HDAC1 Promotes Mitochondrial Pathway Apoptosis and Inhibits the Endoplasmic Reticulum Stress Response in High Glucose-Treated Schwann Cells via Decreased U4 Spliceosomal RNA
Tingting Jin, Ziming Wang, Fan Fan, Wandi Wei, Chenming Zhou, Ziyu Zhang, Yue Gao, Wenhui Li, Lin Zhu, Jun Hao Neurochemical Research.2024; 49(10): 2699. CrossRef - Efficacy of Myricetin Supplementation on Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis of In Vivo Mice Studies
Mihai Babotă, Oleg Frumuzachi, Corneliu Tanase, Andrei Mocan Nutrients.2024; 16(21): 3730. CrossRef -
Detection of polyphenols in carob pods (
Ceratonia siliqua
) from Southern Italy by a lC-HRMS method
Calogero Alfano, Elisa Maria Domenica Messina, Gaetano Cammilleri, Francesco Giuseppe Galluzzo, Licia Pantano, Maria Drussilla Buscemi, Andrea Macaluso, Tiziana Bertuglia, Andrea Pulvirenti, Gianluigi Maria Lo Dico, Ursula M. Jacob, Tilman Fritsch, Vincen Natural Product Research.2024; : 1. CrossRef - Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication?
Yao Chen, Xuejiao Qie, Wei Quan, Maomao Zeng, Fang Qin, Jie Chen, Benu Adhikari, Zhiyong He Critical Reviews in Food Science and Nutrition.2023; 63(20): 4288. CrossRef - Regulation of reactive oxygen species by phytochemicals for the management of cancer and diabetes
Heui Min Lim, See-Hyoung Park Critical Reviews in Food Science and Nutrition.2023; 63(22): 5911. CrossRef - Bioactive compounds from Polygonatum genus as anti-diabetic agents with future perspectives
Yan Shi, Dun Si, Donghong Chen, Xinfeng Zhang, Zhigang Han, Qiang Yu, Jingjing Liu, Jinping Si Food Chemistry.2023; 408: 135183. CrossRef - Venom Peptides, Polyphenols and Alkaloids: Are They the Next Antidiabetics That Will Preserve β-Cell Mass and Function in Type 2 Diabetes?
Michele Lodato, Valérie Plaisance, Valérie Pawlowski, Maxime Kwapich, Alexandre Barras, Emeline Buissart, Stéphane Dalle, Sabine Szunerits, Jérôme Vicogne, Rabah Boukherroub, Amar Abderrahmani Cells.2023; 12(6): 940. CrossRef - TFP5 attenuates cyclin‐dependent kinase 5‐mediated islet β‐cell damage in diabetes
Shunyao Liu, Bo Li, Danna Ma, Yuejia Tao, Jiang Song, Li Bao, Guoqing Zhang, Hongyan Luo, Shilu Cao, Jing E, Yali Zheng Chemical Biology & Drug Design.2023; 102(1): 76. CrossRef - Antiviral and Possible Prophylactic Significance of Myricetin for COVID-19
Pawan K. Agrawal, Chandan Agrawal, Gerald Blunden Natural Product Communications.2023;[Epub] CrossRef - In Vitro and In Silico Protocols for the Assessment of Anti-Tick Compounds from Pinus roxburghii against Rhipicephalus (Boophilus) microplus Ticks
Sana Ayub, Nosheen Malak, Raquel Cossío-Bayúgar, Nasreen Nasreen, Afshan Khan, Sadaf Niaz, Adil Khan, Abdallah D. Alanazi, Mourad Ben Said Animals.2023; 13(8): 1388. CrossRef - Protective Effect of Myricetin Against Experimentally Induced Torsion in Rats
M. Tatar, Z. Polat, J. Öner, H. Öner Biology Bulletin.2023; 50(6): 1338. CrossRef - The pharmacological mechanism of Abelmoschus manihot in the treatment of chronic kidney disease
Cuiting Wei, Chao Wang, Run Li, Yunfeng Bai, Xue Wang, Qingyun Fang, Xiangmei Chen, Ping Li Heliyon.2023; 9(11): e22017. CrossRef - Natural Polyphenols as SERCA Activators: Role in the Endoplasmic Reticulum Stress-Related Diseases
Jana Viskupicova, Petronela Rezbarikova Molecules.2022; 27(16): 5095. CrossRef - Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus
SuFang You, JingYi Zheng, YuPing Chen, HuiBin Huang Frontiers in Endocrinology.2022;[Epub] CrossRef - Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
Huaiyue Hu, Zhiqiang Hu, Yingying Zhang, Hongping Wan, Zhongqiong Yin, Lixia Li, Xiaoxia Liang, Xinghong Zhao, Lizi Yin, Gang Ye, Yuan-Feng Zou, Huaqiao Tang, Renyong Jia, Yaqin Chen, Hao Zhou, Xu Song Frontiers in Microbiology.2022;[Epub] CrossRef - Effects of myricetin against cadmium-induced neurotoxicity in PC12 cells
Azadeh Aminzadeh, Ayda Salarinejad Toxicology Research.2021; 10(1): 84. CrossRef - Pioglitazone-induced AMPK-Glutaminase-1 prevents high glucose-induced pancreatic β-cell dysfunction by glutathione antioxidant system
Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Kyu Chang Won Redox Biology.2021; 45: 102029. CrossRef - Chlorogenic acid and β-glucan from highland barley grain ameliorate β-cell dysfunction via inhibiting apoptosis and improving cell proliferation
Ze-Hua Liu, Bo Li Food & Function.2021; 12(20): 10040. CrossRef - The cyclin dependent kinase inhibitor Roscovitine prevents diet-induced metabolic disruption in obese mice
Nabil Rabhi, Kathleen Desevin, Briana Noel Cortez, Ryan Hekman, Jean Z. Lin, Andrew Emili, Stephen R. Farmer Scientific Reports.2021;[Epub] CrossRef - AdipoRon promotes diabetic fracture repair through endochondral ossification-based bone repair by enhancing survival and differentiation of chondrocytes
Zhongyi Wang, Jinxin Tang, Ying Li, Yu Wang, Yanyang Guo, Qisheng Tu, Jake Chen, Chen Wang Experimental Cell Research.2020; 387(2): 111757. CrossRef - A kinase of many talents: non-neuronal functions of CDK5 in development and disease
Samanta Sharma, Piotr Sicinski Open Biology.2020; 10(1): 190287. CrossRef - Mitochondrial dysfunction in the fetoplacental unit in gestational diabetes mellitus
Luis Sobrevia, Paola Valero, Adriana Grismaldo, Roberto Villalobos-Labra, Fabián Pardo, Mario Subiabre, Gael Armstrong, Fernando Toledo, Sofía Vega, Marcelo Cornejo, Gonzalo Fuentes, Reinaldo Marín Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2020; 1866(12): 165948. CrossRef - Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications
Yasaman Taheri, Hafiz Ansar Rasul Suleria, Natália Martins, Oksana Sytar, Ahmet Beyatli, Balakyz Yeskaliyeva, Gulnaz Seitimova, Bahare Salehi, Prabhakar Semwal, Sakshi Painuli, Anuj Kumar, Elena Azzini, Miquel Martorell, William N. Setzer, Alfred Maroyi, BMC Complementary Medicine and Therapies.2020;[Epub] CrossRef - Current Pharmacological Trends on Myricetin
Gudiya Gupta, Mohd Aftab Siddiqui, Mohd Muazzam Khan, Mohd Ajmal, Rabiya Ahsan, Md Azizur Rahaman, Md Afroz Ahmad, Md Arshad, Mohammad Khushtar Drug Research.2020;[Epub] CrossRef - Silencing cyclophilin A improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic β-cells via MAPK/NF-kb signaling pathway
Tangying Li, Huibiao Quan, Huachuan Zhang, Leweihua Lin, Qianying Ou, Kaining Chen Bioengineered.2020; 11(1): 1047. CrossRef - Endoplasmic reticulum stress contributes to NMDA-induced pancreatic β-cell dysfunction in a CHOP-dependent manner
Xiao-Ting Huang, Wei Liu, Yong Zhou, Mei Sun, Chen-Chen Sun, Chen-Yu Zhang, Si-Yuan Tang Life Sciences.2019; 232: 116612. CrossRef - Dapagliflozin rescues endoplasmic reticulum stress-mediated cell death
Ryo Shibusawa, Eijiro Yamada, Shuichi Okada, Yasuyo Nakajima, Claire C. Bastie, Akito Maeshima, Kyoichi Kaira, Masanobu Yamada Scientific Reports.2019;[Epub] CrossRef - Myricetin prevents thapsigargin-induced CDK5-P66Shc signalosome mediated pancreatic β-cell dysfunction
Udayakumar Karunakaran, Ji Eun Lee, Suma Elumalai, Jun Sung Moon, Kyu Chang Won Free Radical Biology and Medicine.2019; 141: 59. CrossRef - CDK5: Key Regulator of Apoptosis and Cell Survival
Rabih Roufayel, Nimer Murshid Biomedicines.2019; 7(4): 88. CrossRef - Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus
Kai Wang, Yu Su, Yuting Liang, Yanhui Song, Liping Wang International Journal of Molecular Sciences.2019; 20(6): 1517. CrossRef
|