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Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance
Yajie Fan, Zhipeng Yan, Tingting Li, Aolin Li, Xinbiao Fan, Zhongwen Qi, Junping Zhang
Diabetes Metab J. 2024;48(1):19-36.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2023.0110
  • 5,904 View
  • 280 Download
  • 5 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   ePub   
Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.

Citations

Citations to this article as recorded by  
  • Association between METS-IR and heart failure: a cross-sectional study
    Xiaozhou Su, Chunli Zhao, Xianwei Zhang
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Insulin–Heart Axis: Bridging Physiology to Insulin Resistance
    Alfredo Caturano, Raffaele Galiero, Erica Vetrano, Celestino Sardu, Luca Rinaldi, Vincenzo Russo, Marcellino Monda, Raffaele Marfella, Ferdinando Carlo Sasso
    International Journal of Molecular Sciences.2024; 25(15): 8369.     CrossRef
  • The web of intrigue: unraveling the role of NETosis within the gut-microbiome-immune-heart axis in acute myocardial infarction and heart failure
    Tai Yasuda, Kate Deans, Aditi Shankar, Robert Chilton
    Cardiovascular Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • Relationship between the Mediterranean Diet and Vascular Function in Subjects with and without Increased Insulin Resistance
    Marta Gómez-Sánchez, Leticia Gómez-Sánchez, Rocío Llamas-Ramos, Emiliano Rodríguez-Sánchez, Luis García-Ortiz, Ruth Martí-Lluch, María Cortés Rodríguez, Inés Llamas-Ramos, Manuel A. Gómez-Marcos
    Nutrients.2024; 16(18): 3106.     CrossRef
  • Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects
    Qin Ru, Yusheng Li, Lin Chen, Yuxiang Wu, Junxia Min, Fudi Wang
    Signal Transduction and Targeted Therapy.2024;[Epub]     CrossRef
  • The Role of Insulin Within the Socio-Psycho-Biological Framework in Type 2 Diabetes—A Perspective from Psychoneuroimmunology
    Anne Wevers, Silvia San Roman-Mata, Santiago Navarro-Ledesma, Leo Pruimboom
    Biomedicines.2024; 12(11): 2539.     CrossRef
  • Targeting Cardiac Fibrosis in Diabetic Heart Failure: The Role of the EZH2, AMPK, and PPAR-γ Pathways (Diabetes Metab J 2024;48:716-29)
    Jooyeop Lee, Joon Ho Moon
    Diabetes & Metabolism Journal.2024; 48(6): 1176.     CrossRef
Original Articles
Others
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Change Profiles and Functional Targets of MicroRNAs in Type 2 Diabetes Mellitus Patients with Obesity
Guanhua Lu, Huanhuan Gao, Zhiyong Dong, Shuwen Jiang, Ruixiang Hu, Cunchuan Wang
Diabetes Metab J. 2023;47(4):559-570.   Published online April 25, 2023
DOI: https://doi.org/10.4093/dmj.2022.0226
  • 2,833 View
  • 108 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed.
Methods
We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared.
Results
Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM.
Conclusion
We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.

Citations

Citations to this article as recorded by  
  • Early changes of microRNAs in blood one month after bariatric surgery
    Guanhua Lu, Huanhuan Gao, Ruixiang Hu, Ji Miao, Zhiyong Dong, Cunchuan Wang, Xinxin Chen
    Diabetology & Metabolic Syndrome.2024;[Epub]     CrossRef
Basic Research
Article image
Long Non-Coding RNA TUG1 Attenuates Insulin Resistance in Mice with Gestational Diabetes Mellitus via Regulation of the MicroRNA-328-3p/SREBP-2/ERK Axis
Xuwen Tang, Qingxin Qin, Wenjing Xu, Xuezhen Zhang
Diabetes Metab J. 2023;47(2):267-286.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0216
  • 4,259 View
  • 215 Download
  • 6 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Long non-coding RNAs (lncRNAs) have been illustrated to contribute to the development of gestational diabetes mellitus (GDM). In the present study, we aimed to elucidate how lncRNA taurine upregulated gene 1 (TUG1) influences insulin resistance (IR) in a high-fat diet (HFD)-induced mouse model of GDM.
Methods
We initially developed a mouse model of HFD-induced GDM, from which islet tissues were collected for RNA and protein extraction. Interactions among lncRNA TUG1/microRNA (miR)-328-3p/sterol regulatory element binding protein 2 (SREBP-2) were assessed by dual-luciferase reporter assay. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA pancreatic β-cell function (HOMA-β), insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and insulinogenic index (IGI) levels in mouse serum were measured through conducting gain- and loss-of-function experiments.
Results
Abundant expression of miR-328 and deficient expression of lncRNA TUG1 and SREBP-2 were characterized in the islet tissues of mice with HFD-induced GDM. LncRNA TUG1 competitively bound to miR-328-3p, which specifically targeted SREBP-2. Either depletion of miR-328-3p or restoration of lncRNA TUG1 and SREBP-2 reduced the FBG, FINS, HOMA-β, and HOMA-IR levels while increasing ISOGTT and IGI levels, promoting the expression of the extracellular signal-regulated kinase (ERK) signaling pathway-related genes, and inhibiting apoptosis of islet cells in GDM mice. Upregulation miR-328-3p reversed the alleviative effects of SREBP-2 and lncRNA TUG1 on IR.
Conclusion
Our study provides evidence that the lncRNA TUG1 may prevent IR following GDM through competitively binding to miR-328-3p and promoting the SREBP-2-mediated ERK signaling pathway inactivation.

Citations

Citations to this article as recorded by  
  • Diabetes and diabetic associative diseases: An overview of epigenetic regulations of TUG1
    Mohammed Ageeli Hakami
    Saudi Journal of Biological Sciences.2024; 31(5): 103976.     CrossRef
  • Effect of Tinospora cordifolia on gestational diabetes mellitus and its complications
    Ritu Rani, Havagiray Chitme, Avinash Kumar Sharma
    Women & Health.2023; 63(5): 359.     CrossRef
  • Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model
    Ritu Rani, Avinash Kumar Sharma, Havagiray R Chitme
    Clinical Medicine Insights: Endocrinology and Diabetes.2023;[Epub]     CrossRef
  • The role of ncRNA regulatory mechanisms in diseases—case on gestational diabetes
    Dong Gao, Liping Ren, Yu-Duo Hao, Nalini Schaduangrat, Xiao-Wei Liu, Shi-Shi Yuan, Yu-He Yang, Yan Wang, Watshara Shoombuatong, Hui Ding
    Briefings in Bioinformatics.2023;[Epub]     CrossRef
  • lncRNA TUG1 as Potential Novel Biomarker for Prognosis of Cardiovascular Diseases
    Habib Haybar, Narjes Sadat Sadati, Daryush Purrahman, Mohammad Reza Mahmoudian-Sani, Najmaldin Saki
    Epigenomics.2023; 15(23): 1273.     CrossRef
Type 1 Diabetes
Article image
Differential Profile of Plasma Circular RNAs in Type 1 Diabetes Mellitus
Yangyang Li, Ying Zhou, Minghui Zhao, Jing Zou, Yuxiao Zhu, Xuewen Yuan, Qianqi Liu, Hanqing Cai, Cong-Qiu Chu, Yu Liu
Diabetes Metab J. 2020;44(6):854-865.   Published online July 13, 2020
DOI: https://doi.org/10.4093/dmj.2019.0151
  • 7,114 View
  • 155 Download
  • 24 Web of Science
  • 23 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

No currently available biomarkers or treatment regimens fully meet therapeutic needs of type 1 diabetes mellitus (T1DM). Circular RNA (circRNA) is a recently identified class of stable noncoding RNA that have been documented as potential biomarkers for various diseases. Our objective was to identify and analyze plasma circRNAs altered in T1DM.

Methods

We used microarray to screen differentially expressed plasma circRNAs in patients with new onset T1DM (n=3) and age-/gender-matched healthy controls (n=3). Then, we selected six candidates with highest fold-change and validated them by quantitative real-time polymerase chain reaction in independent human cohort samples (n=12). Bioinformatic tools were adopted to predict putative microRNAs (miRNAs) sponged by these validated circRNAs and their downstream messenger RNAs (mRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to gain further insights into T1DM pathogenesis.

Results

We identified 68 differentially expressed circRNAs, with 61 and seven being up- and downregulated respectively. Four of the six selected candidates were successfully validated. Curations of their predicted interacting miRNAs revealed critical roles in inflammation and pathogenesis of autoimmune disorders. Functional relations were visualized by a circRNA-miRNA-mRNA network. GO and KEGG analyses identified multiple inflammation-related processes that could be potentially associated with T1DM pathogenesis, including cytokine-cytokine receptor interaction, inflammatory mediator regulation of transient receptor potential channels and leukocyte activation involved in immune response.

Conclusion

Our study report, for the first time, a profile of differentially expressed plasma circRNAs in new onset T1DM. Further in silico annotations and bioinformatics analyses supported future application of circRNAs as novel biomarkers of T1DM.

Citations

Citations to this article as recorded by  
  • Non-coding RNAs and exosomal non-coding RNAs in diabetic retinopathy: A narrative review
    Yuhong Zhong, Juan Xia, Li Liao, Mohammad Reza Momeni
    International Journal of Biological Macromolecules.2024; 259: 128182.     CrossRef
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    Ren-Jie Zhao, Wan-Ying Zhang, Xing-Xing Fan
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    Ziwei Zhang, Shuoming Luo, Zilin Xiao, Wenfeng Yin, Xiajie Shi, Hongzhi Chen, Zhiguo Xie, Zhenqi Liu, Xia Li, Zhiguang Zhou
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    Pengqiang Zhong, Lu Bai, Mengzhi Hong, Juan Ouyang, Ruizhi Wang, Xiaoli Zhang, Peisong Chen
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    Lucyna Stachowiak, Weronika Kraczkowska, Aleksandra Świercz, Paweł Piotr Jagodziński
    Biochemical and Biophysical Research Communications.2024; 736: 150482.     CrossRef
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    Manuela Cabiati, Giovanni Federico, Silvia Del Ry
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    Zi Li, Yuanyuan Ren, Ziwei Lv, Man Li, Yujia Li, Xiaobin Fan, Yuyan Xiong, Lu Qian
    Biomedicine & Pharmacotherapy.2023; 168: 115744.     CrossRef
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Short Communication
Clinical Diabetes & Therapeutics
Three Months Monitored Metabolic Fitness Modulates Cardiovascular Risk Factors in Diabetic Patients
Ilenia Cirilli, Sonia Silvestri, Fabio Marcheggiani, Fabiola Olivieri, Roberta Galeazzi, Roberto Antonicelli, Rina Recchioni, Fiorella Marcheselli, Tiziana Bacchetti, Luca Tiano, Patrick Orlando
Diabetes Metab J. 2019;43(6):893-897.   Published online June 27, 2019
DOI: https://doi.org/10.4093/dmj.2018.0254
  • 4,762 View
  • 54 Download
  • 11 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   

Cardiovascular diseases represent the leading cause of death and moderate physical exercise is associated with a reduction in cardiovascular risk. The aim of the study was to evaluate the correlation between the amount of exercise recorded daily by a wearable gravitometer for 3 months and selected biochemical and clinical parameters. Nineteen sedentary type 2 diabetics were recruited and distributed into three homogenous groups, low, medium, and high exercise, according to the level of physical exercise monitored and expressed as MOVEs. Data showed an inverse correlation between MOVEs and oxidative stress indexes and a significant improvement in paraoxonase-1 activities and endothelial functionality. Decrease of visceral/total adipose tissue ratio, systolic blood pressure and a down-regulation of the inflammatory microRNA-146a in high exercise group were observed. Finally, a decrease of glycosylated hemoglobin and an up-regulation of the angiogenic microRNA-130a in medium exercise one was obtained. In this study, precise daily monitoring permitted to underline the importance of the amount of physical activity to counteract some cardiovascular risk factors persisting in diabetes. Finally, it identifies new microRNA biomarkers for future investigation on the same topic.

Citations

Citations to this article as recorded by  
  • Emerging roles of microRNAs as diagnostics and potential therapeutic interest in type 2 diabetes mellitus
    Dharmsheel Shrivastav, Desh Deepak Singh
    World Journal of Clinical Cases.2024; 12(3): 525.     CrossRef
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    Karolina Biernat, Natalia Kuciel, Justyna Mazurek, Katarzyna Hap
    Life.2024; 14(5): 616.     CrossRef
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    Moomna Afzal, Francesca Greco, Federico Quinzi, Francesca Scionti, Samantha Maurotti, Tiziana Montalcini, Annamaria Mancini, Pasqualina Buono, Gian Pietro Emerenziani
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    Yang Chen, Xingsheng Jin, Guochong Chen, Ru Wang, Haili Tian
    JMIR Public Health and Surveillance.2024; 10: e54318.     CrossRef
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    Waleska Dornas, Maisa Silva
    Nutrition, Metabolism and Cardiovascular Diseases.2024;[Epub]     CrossRef
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Original Article
Technology/Device
Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy
In-Hwa Park, Yi-Sun Song, Hyun-Woo Joo, Guang-Yin Shen, Jin-Hee Seong, Na-Kyoung Shin, Young Jong Cho, Yonggu Lee, Jeong Hun Shin, Young-Hyo Lim, Hyuck Kim, Kyung-Soo Kim
Diabetes Metab J. 2020;44(1):173-185.   Published online April 23, 2019
DOI: https://doi.org/10.4093/dmj.2018.0211
  • 6,307 View
  • 81 Download
  • 13 Web of Science
  • 11 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.

Methods

Rats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.

Results

G-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.

Conclusion

Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.

Citations

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    Shiva Roshankhah, Ahmad Shabanizadeh, Amir Abdolmaleki, Mohammad Reza Gholami, Mohammad Reza Salahshoor
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    N. A. Koziolova, P. G. Karavaev, A. S. Veklich
    South Russian Journal of Therapeutic Practice.2020; 1(2): 93.     CrossRef
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    Jin Hwa Kim
    Diabetes & Metabolism Journal.2020; 44(1): 54.     CrossRef

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