Diabetes & Metabolism Journal

2020

Original Articles

Obesity and Metabolic Syndrome
PF-04620110, a Potent Antidiabetic Agent, Suppresses Fatty Acid-Induced NLRP3 Inflammasome Activation in Macrophages: Seung Il Jo, Jung Hwan Bae, Seong Jin Kim, Jong Min Lee, Ji Hun Jeong, Jong-Seok Moon; Diabetes Metab J. 2019;43(5):683-699. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0112

4,828 View
64 Download
1 Citations

Abstract PDF Supplementary Material PubReader

Background

Chronic inflammation has been linked to insulin resistance and type 2 diabetes mellitus (T2DM). High-fat diet (HFD)-derived fatty acid is associated with the activation of chronic inflammation in T2DM. PF-04620110, which is currently in phase 1 clinical trials as a selective acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) inhibitor, is a potent anti-diabetic agent that may be important for the regulation of chronic inflammation in T2DM. However, the mechanisms by which PF-04620110 regulates fatty acid-induced chronic inflammation remain unclear.

Methods

PF-04620110 was used in vitro and in vivo. DGAT1-targeting gRNAs were used for deletion of mouse DGAT1 via CRISPR ribonucleoprotein (RNP) system. The activation of NLRP3 inflammasome was measured by immunoblot or cytokine analysis in vitro and in vivo.

Results

Here we show that PF-04620110 suppressed fatty acid-induced nucleotide-binding domain, leucine-rich-repeat-containing receptor (NLR), pyrin-domain-containing 3 (NLRP3) inflammasome activation in macrophages. In contrast, PF-04620110 did not change the activation of the NLR family, CARD-domain-containing 4 (NLRC4), or the absent in melanoma 2 (AIM2) inflammasomes. Moreover, PF-04620110 inhibited K⁺ efflux and the NLRP3 inflammasome complex formation, which are required for NLRP3 inflammasome activation. PF-04620110 reduced the production of interleukin 1β (IL-1β) and IL-18 and blood glucose levels in the plasma of mice fed HFD. Furthermore, genetic inhibition of DGAT1 suppressed fatty acid-induced NLRP3 inflammasome activation.

Conclusion

Our results suggest that PF-04620110 suppresses fatty acid-induced NLRP3 inflammasome activation.

Citations

Citations to this article as recorded by

Possible therapeutic targets for NLRP3 inflammasome-induced breast cancer
Xixi Wang, Junyi Lin, Zhe Wang, Zhi Li, Minghua Wang
Discover Oncology.2023;[Epub] CrossRef

Pathophysiology
Essential Role of Protein Arginine Methyltransferase 1 in Pancreas Development by Regulating Protein Stability of Neurogenin 3: Kanghoon Lee, Hyunki Kim, Joonyub Lee, Chang-Myung Oh, Heein Song, Hyeongseok Kim, Seung-Hoi Koo, Junguee Lee, Ajin Lim, Hail Kim; Diabetes Metab J. 2019;43(5):649-658. Published online April 8, 2019; DOI: https://doi.org/10.4093/dmj.2018.0232

4,488 View
64 Download
5 Citations

Abstract PDF PubReader

Background

Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells. Recent studies have revealed that PRMT1 plays important roles in the development of various tissues. However, its role in pancreas development has not yet been elucidated.

Methods

Pancreatic progenitor cell-specific Prmt1 knock-out (Prmt1 PKO) mice were generated and characterized for their metabolic and histological phenotypes and their levels of Neurog3 gene expression and neurogenin 3 (NGN3) protein expression. Protein degradation assays were performed in mPAC cells.

Results

Prmt1 PKO mice showed growth retardation and a severely diabetic phenotype. The pancreatic size and β-cell mass were significantly reduced in Prmt1 PKO mice. Proliferation of progenitor cells during the secondary transition was decreased and endocrine cell differentiation was impaired. These defects in pancreas development could be attributed to the sustained expression of NGN3 in progenitor cells. Protein degradation assays in mPAC cells revealed that PRMT1 was required for the rapid degradation of NGN3.

Conclusion

PRMT1 critically contributes to pancreas development by destabilizing the NGN3 protein.

Citations

Citations to this article as recorded by

Arginine 65 methylation of Neurogenin 3 by PRMT1 is required for pancreatic endocrine development of hESCs
Gahyang Cho, Kwangbeom Hyun, Jieun Choi, Eunji Shin, Bumsoo Kim, Hail Kim, Jaehoon Kim, Yong-Mahn Han
Experimental & Molecular Medicine.2023; 55(7): 1506. CrossRef
Protein arginine methyltransferase 1 in the generation of immune megakaryocytes: A perspective review
Xinyang Zhao, Zechen Chong, Yabing Chen, X. Long Zheng, Qian-Fei Wang, Yueying Li
Journal of Biological Chemistry.2022; 298(11): 102517. CrossRef
Arginine 65 Methylation of Neurogenin 3 by PRMT1 Is Required for Pancreatic Endocrine Development of hESCs
Gahyang Cho, Kwangbeom Hyun, Jieun Choi, Eun Ji Shin, Bumsoo Kim, Hail Kim, Jaehoon Kim, Yong-Mahn Han
SSRN Electronic Journal .2022;[Epub] CrossRef
Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
Sahar Waseem, Sudeep Kumar, Kanghoon Lee, Byoung-Ha Yoon, Mirang Kim, Hail Kim, Keesook Lee
International Journal of Molecular Sciences.2021; 22(15): 7951. CrossRef
Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis
Meijin Wei, Chaochao Tan, Zhouqin Tang, Yingying Lian, Ying Huang, Yi Chen, Congwei Chen, Wen Zhou, Tao Cai, Jiliang Hu
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef

Clinical Diabetes & Therapeutics
Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials: Yu Mi Kang, Yun Kyung Cho, Jiwoo Lee, Seung Eun Lee, Woo Je Lee, Joong-Yeol Park, Ye-Jee Kim, Chang Hee Jung, Michael A. Nauck; Diabetes Metab J. 2019;43(4):410-421. Published online December 27, 2018; DOI: https://doi.org/10.4093/dmj.2018.0070

5,520 View
126 Download
17 Citations

Abstract PDF Supplementary Material PubReader

Background

Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit.

Methods

Three CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed.

Results

Overall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001).

Conclusion

Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.

Citations

Citations to this article as recorded by

Coronary Artery Disease in South Asian Patients: Cardiovascular Risk Factors, Pathogenesis and Treatments
Vincenzo Sucato, Giuseppe Coppola, Girolamo Manno, Giuseppe Vadalà, Giuseppina Novo, Egle Corrado, Alfredo Ruggero Galassi
Current Problems in Cardiology.2023; 48(8): 101228. CrossRef
Retrospective Analysis of the Effectiveness of Oral Semaglutide in Type 2 Diabetes Mellitus and Its Effect on Cardiometabolic Parameters in Japanese Clinical Settings
Hodaka Yamada, Masashi Yoshida, Shunsuke Funazaki, Jun Morimoto, Shiori Tonezawa, Asuka Takahashi, Shuichi Nagashima, Kimura Masahiko, Otsuka Kiyoshi, Kazuo Hara
Journal of Cardiovascular Development and Disease.2023; 10(4): 176. CrossRef
Efficacy of treatment with glucagon-like peptide receptor agonists-1 in Asian patients with type 2 diabetes mellitus
L. Yu. Khamnueva, L. S. Andreeva
Problems of Endocrinology.2023; 69(2): 38. CrossRef
Role of diabetes in stroke: Recent advances in pathophysiology and clinical management
Sian A. Bradley, Kevin J. Spring, Roy G. Beran, Dimitrios Chatzis, Murray C. Killingsworth, Sonu M. M. Bhaskar
Diabetes/Metabolism Research and Reviews.2022;[Epub] CrossRef
Obesity Pillars Roundtable: Obesity and East Asians
Harold Edward Bays, Jennifer Ng, Jeffrey Sicat, Michelle Look
Obesity Pillars.2022; 2: 100011. CrossRef
Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations
Calvin Ke, K. M. Venkat Narayan, Juliana C. N. Chan, Prabhat Jha, Baiju R. Shah
Nature Reviews Endocrinology.2022; 18(7): 413. CrossRef
Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)
Timothy M. E. Davis, Anna Giczewska, Yuliya Lokhnygina, Robert J. Mentz, Naveed Sattar, Rury R. Holman
Cardiovascular Diabetology.2022;[Epub] CrossRef
Generalizability of the Results of Cardiovascular Outcome Trials of Glucagon-Like Peptide 1 Receptor Agonists in Chinese Patients with Type 2 Diabetes Mellitus
Xiaoling Cai, Linong Ji
Diabetes Therapy.2021; 12(7): 1861. CrossRef
Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes
Jae-Seung Yun, Seung-Hyun Ko
Metabolism.2021; 123: 154838. CrossRef
Sex and ethnic differences in the cardiovascular complications of type 2 diabetes
Jian L. Yeo, Emer M. Brady, Gerry P. McCann, Gaurav S. Gulsin
Therapeutic Advances in Endocrinology and Metabolism.2021; 12: 204201882110342. CrossRef
Efficacy and Safety of GLP-1 Receptor Agonists in Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Yuan Zhu, Jiao Xu, Dong Zhang, Xingyu Mu, Yi Shi, Shangtao Chen, Zengxiang Wu, Shuangqing Li
Frontiers in Endocrinology.2021;[Epub] CrossRef
Efficacy and safety of dulaglutide in type 2 diabetes patients in endocrinology clinics of Islamabad, Pakistan
Matiullah Kamin, SajjadAli Khan, UmarYousaf Raja, Osama Ishtiaq, Asmara Malik, Tejhmal Rehman, MuhammadUmar Wahab
Indian Journal of Endocrinology and Metabolism.2021; 25(5): 456. CrossRef
Type 2 Diabetes and Atherosclerotic Cardiovascular Disease in South Asians: a Unique Population with a Growing Challenge
Afreen I. Shariff, Nitya Kumar, William S. Yancy, Leonor Corsino
Current Diabetes Reports.2020;[Epub] CrossRef
Antihypertensive and Renal Mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) Inhibitors
Christopher S. Wilcox
Hypertension.2020; 75(4): 894. CrossRef
Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
Liyun He, Na Yang, Lingling Xu, Fan Ping, Wei Li, Yuxiu Li, Huabing Zhang
Diabetes Therapy.2020; 11(9): 2121. CrossRef
2020 Consensus of Taiwan Society of Cardiology on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases
Chern-En Chiang, Kwo-Chang Ueng, Ting-Hsing Chao, Tsung-Hsien Lin, Yih-Jer Wu, Kang-Ling Wang, Shih-Hsien Sung, Hung-I Yeh, Yi-Heng Li, Ping-Yen Liu, Kuan-Cheng Chang, Kou-Gi Shyu, Jin-Long Huang, Cheng-Dao Tsai, Huei-Fong Hung, Ming-En Liu, Tze-Fan Chao,
Journal of the Chinese Medical Association.2020; 83(7): 587. CrossRef
Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease
Kyung-Soo Kim, Byung-Wan Lee
Clinical and Molecular Hepatology.2020; 26(4): 430. CrossRef

Obesity and Metabolic Syndrome
The Risk of Myocardial Infarction and Ischemic Stroke According to Waist Circumference in 21,749,261 Korean Adults: A Nationwide Population-Based Study: Jung-Hwan Cho, Eun-Jung Rhee, Se-Eun Park, Hyemi Kwon, Jin-Hyung Jung, Kyung-Do Han, Yong-Gyu Park, Hye Soon Park, Yang-Hyun Kim, Soon-Jib Yoo, Won-Young Lee; Diabetes Metab J. 2019;43(2):206-221. Published online December 27, 2018; DOI: https://doi.org/10.4093/dmj.2018.0039

5,024 View
100 Download
22 Citations

Abstract PDF Supplementary Material PubReader

Background

Waist circumference (WC) is a well-known obesity index that predicts cardiovascular disease (CVD). We studied the relationship between baseline WC and development of incident myocardial infarction (MI) and ischemic stroke (IS) using a nationwide population-based cohort, and evaluated if its predictability is better than body mass index (BMI).

Methods

Our study included 21,749,261 Koreans over 20 years of age who underwent the Korean National Health Screening between 2009 and 2012. The occurrence of MI or IS was investigated until the end of 2015 using National Health Insurance Service data.

Results

A total of 127,289 and 181,637 subjects were newly diagnosed with MI and IS. The incidence rate and hazard ratio of MI and IS increased linearly as the WC level increased, regardless of adjustment for BMI. When the analyses were performed according to 11 groups of WC, the lowest risk of MI was found in subjects with WC of 70 to 74.9 and 65 to 69.9 cm in male and female, and the lowest risk of IS in subjects with WC of 65 to 69.9 and 60 to 64.9 cm in male and female, respectively. WC showed a better ability to predict CVD than BMI with smaller Akaike information criterion. The optimal WC cutoffs were 84/78 cm for male/female for predicting MI, and 85/78 cm for male/female for predicting IS.

Conclusion

WC had a significant linear relationship with the risk of MI and IS and the risk began to increase from a WC that was lower than expected.

Citations

Citations to this article as recorded by

Body mass index, waist circumference and cardiovascular diseases in transitional ages (40 and 66 years)
Jung Eun Yoo, Kyungdo Han, Jin‐Hyung Jung, Yang‐Im Hur, Yang Hyun Kim, Eun Sook Kim, Jang Won Son, Eun‐Jung Rhee, Won‐Young Lee, Ga Eun Nam
Journal of Cachexia, Sarcopenia and Muscle.2023; 14(1): 369. CrossRef
Risk factors for stroke among anthropometric indices and lipid profiles in the Korean population: a large-scale cross-sectional study
Mi Hong Yim, Young Ju Jeon, Bum Ju Lee
Scientific Reports.2023;[Epub] CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Research on obesity using the National Health Information Database: recent trends
Eun-Jung Rhee
Cardiovascular Prevention and Pharmacotherapy.2023; 5(2): 35. CrossRef
Association between the weight-adjusted waist index and stroke: a cross-sectional study
Jiayi Ye, Yanjie Hu, Xinrong Chen, Zhe Yin, Xingzhu Yuan, Liping Huang, Ka Li
BMC Public Health.2023;[Epub] CrossRef
Increased risk of ischemic stroke associated with elevated gamma-glutamyl transferase level in adult cancer survivors: a population-based cohort study
Kyuwoong Kim, Hyeyun Jung, Edvige Di Giovanna, Tae Joon Jun, Young-Hak Kim
Scientific Reports.2023;[Epub] CrossRef
Usefulness of New Criteria for Metabolic Syndrome Optimized for Prediction of Cardiovascular Diseases in Japanese
Yurie Yamazaki, Kazuya Fujihara, Takaaki Sato, Mayuko Harada Yamada, Yuta Yaguchi, Yasuhiro Matsubayashi, Takaho Yamada, Satoru Kodama, Kiminori Kato, Hitoshi Shimano, Hirohito Sone
Journal of Atherosclerosis and Thrombosis.2023;[Epub] CrossRef
Changes in body composition and subsequent cardiovascular disease risk among 5-year breast cancer survivors
Ji Soo Kim, Jihun Song, Seulggie Choi, Sang Min Park
Frontiers in Cardiovascular Medicine.2023;[Epub] CrossRef
Association between Stroke and Abdominal Obesity in the Middle-Aged and Elderly Korean Population: KNHANES Data from 2011–2019
Jong Yeon Kim, Sung Min Cho, Youngmin Yoo, Taesic Lee, Jong Koo Kim
International Journal of Environmental Research and Public Health.2022; 19(10): 6140. CrossRef
Prevalence of metabolic syndrome and related factors in a large sample of antipsychotic naïve patients with first-episode psychosis: Baseline results from the PAFIP cohort
Nathalia Garrido-Torres, Miguel Ruiz-Veguilla, Luis Alameda, Manuel Canal-Rivero, María Juncal Ruiz, Marcos Gómez-Revuelta, Rosa Ayesa-Arriola, Ana Rubio-García, Benedicto Crespo-Facorro, Javier Vázquez-Bourgon
Schizophrenia Research.2022; 246: 277. CrossRef
Development and validation of risk prediction models for stroke and mortality among patients with type 2 diabetes in northern China
X. Shao, H. Liu, F. Hou, Y. Bai, Z. Cui, Y. Lin, X. Jiang, P. Bai, Y. Wang, Y. Zhang, C. Lu, H. Liu, S. Zhou, P. Yu
Journal of Endocrinological Investigation.2022; 46(2): 271. CrossRef
Neck circumference for predicting the occurrence of future cardiovascular events: A 7.6-year longitudinal study
Tingting Hu, Yun Shen, Weijie Cao, Yiting Xu, Yufei Wang, Xiaojing Ma, Yuqian Bao
Nutrition, Metabolism and Cardiovascular Diseases.2022; 32(12): 2830. CrossRef
A prospective study of waist circumference trajectories and incident cardiovascular disease in China: the Kailuan Cohort Study
Liang Wang, Yujin Lee, Yuntao Wu, Xinyuan Zhang, Cheng Jin, Zhe Huang, Yixin Wang, Zhiyi Wang, Penny Kris-Etherton, Shouling Wu, Xiang Gao
The American Journal of Clinical Nutrition.2021; 113(2): 338. CrossRef
The Repeatedly Elevated Fatty Liver Index Is Associated With Increased Mortality: A Population-Based Cohort Study
Chang-Hoon Lee, Kyung-Do Han, Da Hye Kim, Min-Sun Kwak
Frontiers in Endocrinology.2021;[Epub] CrossRef
Obesity Degree and Glycemic Status: Factors That Should Be Considered in Heart Failure
Hye Soon Kim
Diabetes & Metabolism Journal.2020; 44(4): 529. CrossRef
Exposure-weighted scoring for metabolic syndrome and the risk of myocardial infarction and stroke: a nationwide population-based study
Eun Young Lee, Kyungdo Han, Da Hye Kim, Yong-Moon Park, Hyuk-Sang Kwon, Kun-Ho Yoon, Mee Kyoung Kim, Seung-Hwan Lee
Cardiovascular Diabetology.2020;[Epub] CrossRef
Predicting the Development of Myocardial Infarction in Middle-Aged Adults with Type 2 Diabetes: A Risk Model Generated from a Nationwide Population-Based Cohort Study in Korea
Seung-Hwan Lee, Kyungdo Han, Hun-Sung Kim, Jae-Hyoung Cho, Kun-Ho Yoon, Mee Kyoung Kim
Endocrinology and Metabolism.2020; 35(3): 636. CrossRef
Obesity Fact Sheet in Korea, 2018: Data Focusing on Waist Circumference and Obesity-Related Comorbidities
Ga Eun Nam, Yang-Hyun Kim, Kyungdo Han, Jin-Hyung Jung, Yong Gyu Park, Kwan-Woo Lee, Eun-Jung Rhee, Jang Won Son, Seong-Su Lee, Hyuk-Sang Kwon, Won-Young Lee, Soon Jib Yoo
Journal of Obesity & Metabolic Syndrome.2019; 28(4): 236. CrossRef
Simply the Best: Anthropometric Indices for Predicting Cardiovascular Disease
Jie-Eun Lee
Diabetes & Metabolism Journal.2019; 43(2): 156. CrossRef
Association and Interaction Analysis of Lipid Accumulation Product with Impaired Fasting Glucose Risk: A Cross-Sectional Survey
Jian Song, Xue Chen, Yuhong Jiang, Jing Mi, Yuyuan Zhang, Yingying Zhao, Xuesen Wu, Huaiquan Gao
Journal of Diabetes Research.2019; 2019: 1. CrossRef
Letter: Association of Z-Score of the Log-Transformed A Body Shape Index with Cardiovascular Disease in People Who Are Obese but Metabolically Healthy: The Korea National Health and Nutrition Examination Survey 2007-2010 (J Obes Metab Syndr 2018;27:158-65
Eun-Jung Rhee
Journal of Obesity & Metabolic Syndrome.2019; 28(2): 139. CrossRef
Response: The Differential Association between Muscle Strength and Diabetes Mellitus According to the Presence or Absence of Obesity (J Obes Metab Syndr 2019;28:46-52)
Bo Kyung Koo
Journal of Obesity & Metabolic Syndrome.2019; 28(4): 297. CrossRef

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

4,365 View
92 Download
28 Citations

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.

Citations

Citations to this article as recorded by

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; 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
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.2023; : 101887. 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

Epidemiology
High Proportion of Adult Cases and Prevalence of Metabolic Syndrome in Type 1 Diabetes Mellitus Population in Korea: A Nationwide Study: You-Bin Lee, Kyungdo Han, Bongsung Kim, Sang-Man Jin, Seung-Eun Lee, Ji Eun Jun, Jiyeon Ahn, Gyuri Kim, Jae Hyeon Kim; Diabetes Metab J. 2019;43(1):76-89. Published online August 22, 2018; DOI: https://doi.org/10.4093/dmj.2018.0048

5,116 View
98 Download
23 Citations

Abstract PDF Supplementary Material PubReader

Background

The prevalence and incidence of type 1 diabetes mellitus (T1DM) in all age groups and the prevalence of metabolic syndrome in patients with T1DM in Korea were estimated.

Methods

The incidence and prevalence of T1DM between 2007 and 2013 were calculated using the Korean National Health Insurance Service (NHIS) datasets of claims. Clinical characteristics and prevalence of metabolic syndrome in individuals with T1DM between 2009 and 2013 were determined using the database of NHIS preventive health checkups.

Results

The prevalence of T1DM in Korea between 2007 and 2013 was 0.041% to 0.047%. The annual incidence rate of T1DM in Korea in 2007 to 2013 was 2.73 to 5.02/100,000 people. Although the incidence rate of typical T1DM was highest in teenagers, it remained steady in adults over 30 years of age. In contrast, the incidence rate of atypical T1DM in 2013 was higher in people aged 40 years or older than in younger age groups. Age- and sex-adjusted prevalence of metabolic syndrome in patients with T1DM was 51.65% to 55.06% between 2009 and 2013.

Conclusion

T1DM may be more common in Korean adults than previously believed. Metabolic syndrome may be a frequent finding in individuals with T1DM in Korea.

Citations

Citations to this article as recorded by

Comparison of Insulin-Treated Patients with Ambiguous Diabetes Type with Definite Type 1 and Type 2 Diabetes Mellitus Subjects: A Clinical Perspective
Insa Laspe, Juris J. Meier, Michael A. Nauck
Diabetes & Metabolism Journal.2023; 47(1): 140. CrossRef
Clinical and biochemical profile of childhood–adolescent-onset type 1 diabetes and adult-onset type 1 diabetes among Asian Indians
Viswanathan Mohan, Ganesan Uma Sankari, Anandakumar Amutha, Ranjit Mohan Anjana, Saravanan Jeba Rani, Ranjit Unnikrishnan, Ulagamathesan Venkatesan, Coimbatore Subramanian Shanthi Rani
Acta Diabetologica.2023; 60(4): 579. CrossRef
Subtypes of type 2 diabetes and their association with outcomes in Korean adults - A cluster analysis of community-based prospective cohort
You-Cheol Hwang, Hong-Yup Ahn, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung
Metabolism.2023; 141: 155514. CrossRef
Insulin Fact Sheet in Type 1 and 2 Diabetes Mellitus and Trends of Antidiabetic Medication Use in Insulin Users with Type 2 Diabetes Mellitus: 2002 to 2019
Jiyun Park, Gyuri Kim, Bong-Sung Kim, Kyung-Do Han, So Yoon Kwon, So Hee Park, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim
Diabetes & Metabolism Journal.2023; 47(2): 211. CrossRef
Insulin resistance is more frequent in type 1 diabetes patients with long disease duration
Yuting Xie, Mei Shi, Xiaolin Ji, Fansu Huang, Li Fan, Xia Li, Zhiguang Zhou
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef
Long-term Effectiveness of the National Diabetes Quality Assessment Program in South Korea
Ji Hye Huh, Serim Kwon, Gui Ok Kim, Bo Yeon Kim, Kyoung Hwa Ha, Dae Jung Kim
Diabetes Care.2023; 46(9): 1700. CrossRef
Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus
Qianwen Huang, Daizhi Yang, Hongrong Deng, Hua Liang, Xueying Zheng, Jinhua Yan, Wen Xu, Xiangwen Liu, Bin Yao, Sihui Luo, Jianping Weng
Diabetes & Metabolism Journal.2022; 46(1): 93. CrossRef
The Incidence of Adult-Onset Type 1 Diabetes: A Systematic Review From 32 Countries and Regions
Jessica L. Harding, Pandora L. Wander, Xinge Zhang, Xia Li, Suvi Karuranga, Hongzhi Chen, Hong Sun, Yuting Xie, Richard A. Oram, Dianna J. Magliano, Zhiguang Zhou, Alicia J. Jenkins, Ronald C.W. Ma
Diabetes Care.2022; 45(4): 994. CrossRef
Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus
Jong Ha Baek, Woo Je Lee, Byung-Wan Lee, Soo Kyoung Kim, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Diabetes & Metabolism Journal.2021; 45(1): 46. CrossRef
Genomic ancestry and metabolic syndrome in individuals with type 1 diabetes from an admixed population: a multicentre, cross‐sectional study in Brazil
B. S. V. Barros, D. C. Santos, L. G. N. Melo, M. H. Pizarro, L. H. Muniz, D. A. Silva, L. C. Porto, M. B. Gomes
Diabetic Medicine.2021;[Epub] CrossRef
The Interplay Between Diet and the Epigenome in the Pathogenesis of Type-1 Diabetes
Amira Kohil, Maha Al-Asmakh, Mashael Al-Shafai, Annalisa Terranegra
Frontiers in Nutrition.2021;[Epub] CrossRef
Risk of early mortality and cardiovascular disease according to the presence of recently diagnosed diabetes and requirement for insulin treatment: A nationwide study
You‐Bin Lee, Kyungdo Han, Bongsung Kim, Min Sun Choi, Jiyun Park, Minyoung Kim, Sang‐Man Jin, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim
Journal of Diabetes Investigation.2021; 12(10): 1855. CrossRef
Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus (Diabetes Metab J 2021;45:46-54)
Ye Seul Yang, Tae Seo Sohn
Diabetes & Metabolism Journal.2021; 45(2): 277. CrossRef
Comparison of fracture risk between type 1 and type 2 diabetes: a comprehensive real-world data
J. Ha, C. Jeong, K.-D. Han, Y. Lim, M.K. Kim, H.-S. Kwon, K.-H. Song, M.I. Kang, K.-H. Baek
Osteoporosis International.2021; 32(12): 2543. CrossRef
Early mortality and cardiovascular disease, varied association with body mass index and its changes in insulin-treated diabetes: a nationwide study
You-Bin Lee, Bongsung Kim, Jiyun Park, Minyoung Kim, Min Sun Choi, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Kyungdo Han, Jae Hyeon Kim
International Journal of Obesity.2021; 45(11): 2482. CrossRef
Young-onset type 2 diabetes in South Korea: a review of the current status and unmet need
Ye Seul Yang, Kyungdo Han, Tae Seo Sohn, Nam Hoon Kim
The Korean Journal of Internal Medicine.2021; 36(5): 1049. CrossRef
Positive association between the ratio of triglycerides to high-density lipoprotein cholesterol and diabetes incidence in Korean adults
Joungyoun Kim, Sang-Jun Shin, Ye-Seul Kim, Hee-Taik Kang
Cardiovascular Diabetology.2021;[Epub] CrossRef
Mortality and causes of death in a population with blindness in Korea: A longitudinal follow-up study using a national sample cohort
Hyo Geun Choi, Min Joung Lee, Sang-Mok Lee
Scientific Reports.2020;[Epub] CrossRef
Hospitalization for heart failure incidence according to the transition in metabolic health and obesity status: a nationwide population-based study
You-Bin Lee, Da Hye Kim, Seon Mee Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Yong Gyu Park, Kyungdo Han, Hye Jin Yoo
Cardiovascular Diabetology.2020;[Epub] CrossRef
Management of Type 1 Diabetes Mellitus in Adults
Hye Ryoung Yun
The Journal of Korean Diabetes.2020; 21(3): 156. CrossRef
New Insulin Pumps and Open Source Artificial Pancreas System in Korea
Jae Hyeon Kim
The Journal of Korean Diabetes.2020; 21(4): 197. CrossRef
Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study
You-Bin Lee, Kyungdo Han, Bongsung Kim, Seung-Eun Lee, Ji Eun Jun, Jiyeon Ahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Cardiovascular Diabetology.2019;[Epub] CrossRef
Risk of end‐stage renal disease from chronic kidney disease defined by decreased glomerular filtration rate in type 1 diabetes: A comparison with type 2 diabetes and the effect of metabolic syndrome
You‐Bin Lee, Kyungdo Han, Bongsung Kim, Ji Eun Jun, Seung‐Eun Lee, Jiyeon Ahn, Gyuri Kim, Sang‐Man Jin, Jae Hyeon Kim
Diabetes/Metabolism Research and Reviews.2019;[Epub] CrossRef

First
Prev
Page of 1
Next
Last

Best paper of the year