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Original Articles
- Islet Studies and Transplantation
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- 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
- 5,734 View
- 112 Download
- 36 Web of Science
- 37 Crossref
-
Abstract
PDF
Supplementary Material
PubReader 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.
Methods To 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.
Results Activation 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.Conclusion Myricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.
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Citations
Citations to this article as recorded by
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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
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عائشة أدريس, إبراهيم عزاقة, فاطمة عبدالله
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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 - Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication?
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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
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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; 18(4): 1934578X2311662. 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
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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
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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
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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
- Profiling of secondary metabolite and evaluation of anti-diabetic potency of Crotalaria quinquefolia (L): In-vitro, in-vivo, and in-silico approaches
- Complications
- Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis
- Jaechan Leem, Eun Hee Koh, Jung Eun Jang, Chang-Yun Woo, Jin Sun Oh, Min Jung Lee, Joon-Won Kang, Tae-Hwan Lim, Chang Hee Jung, Woo Je Lee, Joong-Yeol Park, Ki-Up Lee
- Diabetes Metab J. 2015;39(5):414-423. Published online October 22, 2015
- DOI: https://doi.org/10.4093/dmj.2015.39.5.414
- 4,823 View
- 43 Download
- 8 Web of Science
- 9 Crossref
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Abstract
PDFPubReader
Background The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD.
Methods We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery.
Results Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 µmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (
P =0.0028).Conclusion Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD.
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Citations
Citations to this article as recorded by- Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort
Vanessa Schoissengeier, Lina Maqboul, Daniela Weber, Tilman Grune, Alexander Bürkle, Maria Moreno-Villaneuva, Claudio Franceschi, Miriam Capri, Jürgen Bernhard, Olivier Toussaint, Florence Debacq-Chainiaux, Birgit Weinberger, Efstathios S. Gonos, Ewa Siko
iScience.2024; 27(7): 110234. CrossRef - Nanoparticle-driven biosensors for diagnosis of viral hepatitis
Chenggong Zhu, Zhen Xun, Ruijie Fu, Qunfang Huang, Qishui Ou, Yunlei Xianyu, Can Liu
TrAC Trends in Analytical Chemistry.2024; 180: 117985. CrossRef - DECREASE IN SERUM BILIRUBIN AS AN UNFAVORABLE MARKER OF CARDIOVASCULAR DISORDERS
L. M. Strilchuk, O. O. Zimba, I. B. Zhakun
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Qing Yao, Xue Jiang, Longfa Kou, Adelaide T. Samuriwo, He-Lin Xu, Ying-Zheng Zhao
Pharmacological Research.2019; 145: 104256. CrossRef - Evaluation of genetic effect of NOS3 and G×E interaction on the variability of serum bilirubin in a Han Chinese population
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- Serum Ceruloplasmin Level as a Predictor for the Progression of Diabetic Nephropathy in Korean Men with Type 2 Diabetes Mellitus
- Min Jung Lee, Chang Hee Jung, Yu Mi Kang, Jung Eun Jang, Jaechan Leem, Joong-Yeol Park, Woo Je Lee
- Diabetes Metab J. 2015;39(3):230-239. Published online April 22, 2015
- DOI: https://doi.org/10.4093/dmj.2015.39.3.230
- 5,157 View
- 55 Download
- 25 Web of Science
- 26 Crossref
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Abstract
PDFPubReader
Background Oxidative stress is known to be associated with progression of diabetic kidney disease. Ceruloplasmin acts as a pro-oxidant under conditions of severe oxidative stress. Thus, we conducted a longitudinal observational study to evaluate whether the serum ceruloplasmin level is a predictive biomarker for progression of diabetic nephropathy.
Methods A total of 643 Korean men with type 2 diabetes mellitus were enrolled. Serum ceruloplasmin was measured using a nephelometric method. Progression of diabetic nephropathy was defined as transition in albuminuria class (i.e., normoalbuminuria to microalbuminuria, microalbuminuria to macroalbuminuria, or normoalbuminuria to macroalbuminuria) and/or a greater than 2-fold increase of serum creatinine at follow-up compared with the baseline value.
Results During the follow-up period (median, 2.7 years; range, 0.3 to 4.4 years), 49 of 643 patients (7.6%) showed the progression of diabetic nephropathy and three patients (0.5%) developed end-stage renal disease. Baseline ceruloplasmin levels were higher in the progressors than in the nonprogressors (262.6±40.9 mg/L vs. 233.3±37.8 mg/L,
P <0.001). Kaplan-Meier analysis showed a significantly higher incidence of nephropathy progression according to ceruloplasmin tertile (log-rank test,P <0.001). The hazard ratio (HR) for progression of diabetic nephropathy was significantly higher in the highest ceruloplasmin tertile category compared with the lowest ceruloplasmin tertile category, even after adjusting for confounding variables (HR, 3.32; 95% confidence interval, 1.28 to 8.61;P =0.003).Conclusion Baseline serum ceruloplasmin is an independent predictive factor for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.
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Citations
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- Proteomic analysis of urinary exosomes reveals ferroptosis-associated proteins are involved in diabetic nephropathy
- Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea
- Chang-Yun Woo, Ji Yun Jeong, Jung Eun Jang, Jaechan Leem, Chang Hee Jung, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Jung Bok Lee, Ki-Up Lee
- Diabetes Metab J. 2015;39(2):126-131. Published online March 9, 2015
- DOI: https://doi.org/10.4093/dmj.2015.39.2.126
- 5,991 View
- 88 Download
- 23 Web of Science
- 20 Crossref
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Abstract
PDFPubReader
Background Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.
Methods To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.
Results Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.
Conclusion The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.
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