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Jae-Han Jeon  (Jeon JH) 14 Articles
Basic research
Article image
Reducing Oxidative Stress and Inflammation by Pyruvate Dehydrogenase Kinase 4 Inhibition Is Important in Prevention of Renal Ischemia-Reperfusion Injury in Diabetic Mice
Ah Reum Khang, Dong Hun Kim, Min-Ji Kim, Chang Joo Oh, Jae-Han Jeon, Sung Hee Choi, In-Kyu Lee
Diabetes Metab J. 2024;48(3):405-417.   Published online February 1, 2024
DOI: https://doi.org/10.4093/dmj.2023.0196
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  • 255 Download
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury.
Methods
We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station.
Results
Following IR injury in diabetic mice, the expression of PDK4, rather than the other PDK isoforms, was induced with a marked increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This was accompanied by a pronounced ROS activation, as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) production. Notably, sodium dichloroacetate (DCA) attenuated renal IR injury-induced apoptosis which can be attributed to reducing PDK4 expression and PDHE1α phosphorylation levels. DCA or shPdk4 treatment reduced oxidative stress and decreased TNF-α, IL-6, IL-1β, and MCP-1 production after IR or hypoxia-reoxygenation injury.
Conclusion
PDK4 inhibition alleviated renal injury with decreased ROS production and inflammation, supporting a critical role for PDK4 in IR mediated damage. This result indicates another potential target for reno-protection during IR injury; accordingly, the role of PDK4 inhibition needs to be comprehensively elucidated in terms of mitochondrial function during renal IR injury.

Citations

Citations to this article as recorded by  
  • Exploring Renal Pyruvate Metabolism as a Therapeutic Avenue for Diabetic Kidney Injury
    Jaemin Lee
    Diabetes & Metabolism Journal.2024; 48(3): 385.     CrossRef
  • Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs
    Seahyoung Lee
    Antioxidants.2024; 13(6): 656.     CrossRef
SGLT2 Inhibitors and GLP-1 Agonists: A Beacon of Hope for Stroke Prevention in Diabetes
Jae-Han Jeon
Diabetes Metab J. 2024;48(2):213-214.   Published online March 22, 2024
DOI: https://doi.org/10.4093/dmj.2024.0079
  • 1,870 View
  • 223 Download
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Basic Research
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CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice
Jongsu Jeon, Dohyun Lee, Bobae Kim, Bo-Yoon Park, Chang Joo Oh, Min-Ji Kim, Jae-Han Jeon, In-Kyu Lee, Onyu Park, Seoyeong Baek, Chae Won Lim, Dongryeol Ryu, Sungsoon Fang, Johan Auwerx, Kyong-Tai Kim, Hoe-Yune Jung
Diabetes Metab J. 2023;47(5):653-667.   Published online April 26, 2023
DOI: https://doi.org/10.4093/dmj.2022.0244
  • 3,302 View
  • 210 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated.
Methods
KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis.
Results
CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1).
Conclusion
Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Citations

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  • Cyclo His‐Pro Attenuates Muscle Degeneration in Murine Myopathy Models
    Alessia De Masi, Nadège Zanou, Keno Strotjohann, Dohyun Lee, Tanes I. Lima, Xiaoxu Li, Jongsu Jeon, Nicolas Place, Hoe‐Yune Jung, Johan Auwerx
    Advanced Science.2024;[Epub]     CrossRef
Basic Research
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The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
Diabetes Metab J. 2023;47(2):153-163.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0305
  • 5,646 View
  • 402 Download
  • 6 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.

Citations

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  • Synthesis, activatory effects, molecular docking and ADME studies as rabbit muscle pyruvate kinase activators of ureido phenyl substituted 1,4-dihydropyridine derivatives
    Mustafa Oğuzhan Kaya, Tuna Demirci, Ümit Çalışır, Oğuzhan Özdemir, Yeşim Kaya, Mustafa Arslan
    Research on Chemical Intermediates.2024; 50(1): 437.     CrossRef
  • Unraveling the causes of sarcopenia: Roles of neuromuscular junction impairment and mitochondrial dysfunction
    Yanmei Miao, Leiyu Xie, Jiamei Song, Xing Cai, Jinghe Yang, Xinglong Ma, Shaolin Chen, Peng Xie
    Physiological Reports.2024;[Epub]     CrossRef
  • Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases
    Zonghao Qian, Yuzhen Huang, Yucong Zhang, Ni Yang, Ziwei Fang, Cuntai Zhang, Le Zhang
    Frontiers in Genetics.2024;[Epub]     CrossRef
  • Inhibition of Pyruvate Dehydrogenase Kinase 4 Protects Cardiomyocytes from lipopolysaccharide-Induced Mitochondrial Damage by Reducing Lactate Accumulation
    Tangtian Chen, Qiumin Xie, Bin Tan, Qin Yi, Han Xiang, Rui Wang, Qin Zhou, Bolin He, Jie Tian, Jing Zhu, Hao Xu
    Inflammation.2024;[Epub]     CrossRef
  • Effect of resistance training plus enriched probiotic supplement on sestrin2, oxidative stress, and mitophagy markers in elderly male Wistar rats
    Majid Mohabbat, Hamid Arazi
    Scientific Reports.2024;[Epub]     CrossRef
  • Comparison between single-muscle evaluation and cross-sectional area muscle evaluation for predicting the prognosis in patients with oral squamous cell carcinoma: a retrospective cohort study
    Hirotaka Takayama, Takuya Yoshimura, Hajime Suzuki, Yuka Hirano, Masahiro Tezuka, Takayuki Ishida, Kiyohide Ishihata, Marie Amitani, Haruka Amitani, Yasunori Nakamura, Yasushi Imamura, Akio Inui, Norifumi Nakamura
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Resveratrol and Vitamin D: Eclectic Molecules Promoting Mitochondrial Health in Sarcopenia
    Cristina Russo, Maria Stella Valle, Floriana D’Angeli, Sofia Surdo, Lucia Malaguarnera
    International Journal of Molecular Sciences.2024; 25(14): 7503.     CrossRef
  • Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases
    Yue Zhang, Meiyan Sun, Hongxiang Zhao, Zhengyan Wang, Yanan Shi, Jianxin Dong, Kaifang Wang, Xi Wang, Xingyue Li, Haiyan Qi, Xiaoyong Zhao
    International Journal of Nanomedicine.2023; Volume 18: 7559.     CrossRef
Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14)
Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Jae-Han Jeon, Mi Kyung Kim, Keun-Gyu Park
Diabetes Metab J. 2021;45(2):279-280.   Published online March 25, 2021
DOI: https://doi.org/10.4093/dmj.2020.0300
  • 4,515 View
  • 87 Download
  • 1 Crossref
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Citations

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  • A cross-sectional study on the telemedicine usage and glycemic status of diabetic patients during the COVID-19 pandemic
    Novi Sulistia Wati, Pokkate Wongsasuluk, Pradana Soewondo
    Medical Journal of Indonesia.2021; 30(3): 215.     CrossRef
COVID-19
Article image
Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus
Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Yin Young Lee, Nan Hee Cho, Ji-Hyun Lee, Jae-Han Jeon, Yeon-Kyung Choi, Mi Kyung Kim, Keun-Gyu Park
Diabetes Metab J. 2021;45(1):109-114.   Published online December 4, 2020
DOI: https://doi.org/10.4093/dmj.2020.0226
  • 9,875 View
  • 311 Download
  • 25 Web of Science
  • 24 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
This study investigated the impact of social distancing due to coronavirus disease 2019 (COVID-19) on glycemic control in people with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the change in glycosylated hemoglobin level (ΔHbA1c) in people with T2DM who undertook social distancing because of COVID-19. We compared the ΔHbA1c between COVID-19 and non-COVID-19 cohorts that were enrolled at the same time of year. The ΔHbA1c of the COVID-19 cohort was significantly higher than that of two non-COVID-19 cohorts. Subgroup analysis according to age and baseline HbA1c level showed that social distancing significantly increased the mean HbA1c level of participants of <50 years. The ΔHbA1c of participants of <50 years and with HbA1c <7.0% in the COVID-19 cohort showed larger changes than other subgroups. In adjusted model, adjusted ΔHbA1c levels in the COVID-19 cohort remained significantly higher than those in the two other cohorts. Social distancing negatively impacts blood glucose control in people with T2DM, especially those who are younger and have good blood glucose control.

Citations

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  • Impact of two COVID-19 lockdowns on HbA1c levels in patients with type 2 diabetes and associations with patient characteristics: a multicentre, observational cohort study over three years
    Ingmar Schäfer, Daniel Tajdar, Laura Walther, Lasse Bittner, Dagmar Lühmann, Martin Scherer
    Frontiers in Public Health.2024;[Epub]     CrossRef
  • Influence of the COVID-19 pandemic on the achievement of guideline targets for HbA1c, blood pressure, and LDL cholesterol in people with diabetes in Japan
    Shingo Kuwajima, Takahito Itoh, Tatsuya Sato, Shoya Ino, Satoru Shibata, Kouhei Ohno, Hiroyuki Hotta, Tomoaki Matsumoto, Hitoshi Ooiwa, Hirofumi Kubo, Takayuki Miki
    Diabetology International.2024;[Epub]     CrossRef
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    Chandana Wijeweera, Ummul Muhfaza, Reginald V. Lord, Peter Petocz, Juliana Chen, Veronica Preda
    Primary Care Diabetes.2024; 18(3): 308.     CrossRef
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    Abdulbari Bener, Murat Atmaca, Abdulla O. A. A. Al-Hamaq, Antonio Ventriglio
    Brain Sciences.2024; 14(4): 377.     CrossRef
  • Self-Care of Adults with Type 2 Diabetes During the COVID-19 Pandemic: A Qualitative Interpretive Description Study
    Michela Luciani, Camilla Bigoni, Marta Canesi, Matteo Masotto, Diletta Fabrizi, Stefania Di Mauro, Davide Ausili
    Clinical Nursing Research.2023; 32(1): 73.     CrossRef
  • Changes in body weight and glycemic control in association with COVID-19 Shutdown among 23,000 adults with type 2 diabetes
    Emily Panza, Kevin E. Kip, Kripa Venkatakrishnan, Oscar C. Marroquin, Rena R. Wing
    Acta Diabetologica.2023; 60(6): 787.     CrossRef
  • The Impact of a Lockdown for the COVID-19 Pandemic on Seasonal HbA1c Variation in Patients with Type 2 Diabetes
    Yu-Cheng Cheng, Yu-Hsuan Li, Hsiu-Chen Liu, Chiann-Yi Hsu, Wan-Jen Chang, I-Te Lee, Chin-Li Lu
    Life.2023; 13(3): 763.     CrossRef
  • Changes in the mean incidence and variance of orthopedic diseases before and during the COVID-19 pandemic in Korea: a retrospective study
    Joo-Hee Kim, Mi Jung Kwon, Hyo Geun Choi, Sang Jun Lee, Sangwon Hwang, Jaemin Lee, San-Hui Lee, Jung Woo Lee
    BMC Musculoskeletal Disorders.2023;[Epub]     CrossRef
  • Gender differences-based bioinformatics analysis to identify hub genes and key pathways in type 2 diabetes
    Md Sojib Hossain, Subrina Islam Rupa, Md Sumon Sarkar, Md Al Amin, Mst Tania Khatun, Md Shamim, Md Zahidul Islam
    Informatics in Medicine Unlocked.2023; 40: 101302.     CrossRef
  • Retrospective Study on the Impact of COVID-19 Lockdown on Patients with Type 2 Diabetes in Northern Taiwan
    Hsuan Huang, Hsiao-Ling Su, Chih-Hsung Huang, Yi-Hsin Lin
    Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 2539.     CrossRef
  • Understanding impacts of COVID-19 restrictions on glycemic control for patients with diabetes in Japan
    Kiyoko Uno-Eder, Noriko Satoh-Asahara, Manabu Hibiya, Kenji Uno, Takuya Uchino, Koji Morita, Toshio Ishikawa, Tetsuji Kaneko, Hajime Yamakage, Yuki Kitaoka, Tomohiro Sawa, Kazuhisa Tsukamoto, Tamio Teramoto
    Journal of Diabetes & Metabolic Disorders.2023; 22(2): 1695.     CrossRef
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    Minal R. Patel, Guanghao Zhang, Cindy Leung, Peter X.K. Song, Michele Heisler, Hae Mi Choe, Roshanak Mehdipanah, Xu Shi, Kenneth Resnicow, Geila Rajaee, John D. Piette
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    Omorogieva Ojo, Xiao-Hua Wang, Osarhumwese Osaretin Ojo, Edith Orjih, Nivedita Pavithran, Amanda Rodrigues Amorim Adegboye, Qian-Qian Feng, Paul McCrone
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    Caroline Cummings, Kagnica Seng, Ryan Tweet, Julie Wagner
    Frontiers in Clinical Diabetes and Healthcare.2022;[Epub]     CrossRef
  • Substitution of telemedicine for clinic visit during the COVID‐19 pandemic of 2020: Comparison of telemedicine and clinic visit
    Yukiko Onishi, Rieko Ichihashi, Yoko Yoshida, Tazu Tahara, Takako Kikuchi, Toshiko Kobori, Tetsuya Kubota, Masahiko Iwamoto, Shoko Hamano, Masato Kasuga
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    Clinical Epidemiology.2022; Volume 14: 1363.     CrossRef
  • Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14)
    Junghyun Noh
    Diabetes & Metabolism Journal.2021; 45(2): 275.     CrossRef
  • Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14)
    Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Jae-Han Jeon, Mi Kyung Kim, Keun-Gyu Park
    Diabetes & Metabolism Journal.2021; 45(2): 279.     CrossRef
  • Glucose control in diabetes during home confinement for the first pandemic wave of COVID-19: a meta-analysis of observational studies
    Giovanni Antonio Silverii, Chiara Delli Poggi, Ilaria Dicembrini, Matteo Monami, Edoardo Mannucci
    Acta Diabetologica.2021; 58(12): 1603.     CrossRef
  • The impact of COVID-19 pandemic on glycemic control in patients with diabetes mellitus in Turkey: a multi-center study from Kocaeli
    Alev Selek, Emre Gezer, Eda Altun, Mehmet Sözen, Ömercan Topaloğlu, Damla Köksalan, Halil Demirkan, Dilek Karakaya, Berrin Cetinarslan, Zeynep Cantürk, Dilek Taymez
    Journal of Diabetes & Metabolic Disorders.2021; 20(2): 1461.     CrossRef
  • Effects of Social Distancing on Diabetes Management in Older Adults during COVID-19 Pandemic
    Soo Myoung Shin, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang
    Diabetes & Metabolism Journal.2021; 45(5): 765.     CrossRef
  • Year-Long Trend in Glycated Hemoglobin Levels in Patients with Type 2 Diabetes during the COVID-19 Pandemic
    Jonghwa Jin, Seong Wook Lee, Won-Ki Lee, Jae-Han Jeon, Jung-Guk Kim, In-Kyu Lee, Yeon-Kyung Choi, Keun-Gyu Park
    Endocrinology and Metabolism.2021; 36(5): 1142.     CrossRef
Covid-19
Article image
The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Mi Kyung Kim, Jae-Han Jeon, Sung-Woo Kim, Jun Sung Moon, Nan Hee Cho, Eugene Han, Ji Hong You, Ji Yeon Lee, Miri Hyun, Jae Seok Park, Yong Shik Kwon, Yeon-Kyung Choi, Ki Tae Kwon, Shin Yup Lee, Eon Ju Jeon, Jin-Woo Kim, Hyo-Lim Hong, Hyun Hee Kwon, Chi Young Jung, Yin Young Lee, Eunyeoung Ha, Seung Min Chung, Jian Hur, June Hong Ahn, Na-young Kim, Shin-Woo Kim, Hyun Ha Chang, Yong Hoon Lee, Jaehee Lee, Keun-Gyu Park, Hyun Ah Kim, Ji-Hyun Lee
Diabetes Metab J. 2020;44(4):602-613.   Published online August 12, 2020
DOI: https://doi.org/10.4093/dmj.2020.0146
  • 13,987 View
  • 212 Download
  • 71 Web of Science
  • 81 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes.

Methods

We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group.

Results

Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease.

Conclusion

DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

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    Gerontology.2023; 69(10): 1200.     CrossRef
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Epidemiology
Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes
Sung Woo Kim, Jae-Han Jeon, Jun Sung Moon, Eon Ju Jeon, Mi-Kyung Kim, In-Kyu Lee, Jung Beom Seo, Keun-Gyu Park
Diabetes Metab J. 2019;43(5):718-726.   Published online March 19, 2019
DOI: https://doi.org/10.4093/dmj.2018.0222
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AbstractAbstract PDFSupplementary MaterialPubReader   

Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

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
  • 5,386 View
  • 111 Download
  • 36 Web of Science
  • 37 Crossref
AbstractAbstract 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.

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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Obesity and Metabolic Syndrome
Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism
Sungmi Park, Jae-Han Jeon, Byong-Keol Min, Chae-Myeong Ha, Themis Thoudam, Bo-Yoon Park, In-Kyu Lee
Diabetes Metab J. 2018;42(4):270-281.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0101
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AbstractAbstract PDFPubReader   

Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.

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Letter: Patient Understanding of Hypoglycemia in Tertiary Referral Centers (Diabetes Metab J 2018;42:43-52)
Jae-Han Jeon
Diabetes Metab J. 2018;42(2):173-174.   Published online April 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.42.2.173
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Complications
Renoprotective Effect of Gemigliptin, a Dipeptidyl Peptidase-4 Inhibitor, in Streptozotocin-Induced Type 1 Diabetic Mice
Gwon-Soo Jung, Jae-Han Jeon, Mi Sun Choe, Sung-Woo Kim, In-Kyu Lee, Mi-Kyung Kim, Keun-Gyu Park
Diabetes Metab J. 2016;40(3):211-221.   Published online March 31, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.3.211
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  • 55 Download
  • 22 Web of Science
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AbstractAbstract PDFPubReader   
Background

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the treatment of patients with type 2 diabetes and have proven protective effects on diabetic kidney disease (DKD). Whether DPP-4 inhibitors have renoprotective effects on insulin-deficient type 1 diabetes has not been comprehensively examined. The aim of this study was to determine whether gemigliptin, a new DPP-4 inhibitor, has renoprotective effects in streptozotocin (STZ)-induced type 1 diabetic mice.

Methods

Diabetes was induced by intraperitoneal administration of a single dose of STZ. Mice with diabetes were treated without or with gemigliptin (300 mg/kg) for 8 weeks. Morphological changes of the glomerular basement membrane (GBM) were observed by electron microscopy and periodic-acid Schiff staining. In addition, we measured blood glucose and urinary albumin excretion and evaluated fibrotic markers using immunohistochemical staining, quantitative reverse transcription polymerase chain reaction analysis, and Western blot analysis.

Results

Gemigliptin did not reduce the blood glucose levels of STZ-treated mice. In gemigliptin-treated mice with STZ, a significant reduction in urinary albumin excretion and GBM thickness was observed. Immunohistological examination revealed that gemigliptin attenuated renal fibrosis induced by STZ and decreased extracellular matrix protein levels, including those of type I collagen and fibronectin, and Smad3 phosphorylation. In cultured rat renal cells, gemigliptin inhibited transforming growth factor β-stimulated type I collagen and fibronectin mRNA and protein levels via down-regulation of Smad3 phosphorylation.

Conclusion

Our data demonstrate that gemigliptin has renoprotective effects on DKD, regardless of its glucose-lowering effect, suggesting that it could be used to prevent DKD, including in patients with type 1 diabetes.

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