Endocrinology and Metabolism

Dinh Vinh Do

2 Articles

Diabetes, Obesity and Metabolism
Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction: Giang Nguyen, So Young Park, Dinh Vinh Do, Dae-Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2022;37(6):918-928. Published online November 15, 2022; DOI: https://doi.org/10.3803/EnM.2022.1530

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Background
Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis.
Methods
To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol–induced mouse model of nonalcoholic steatohepatitis (NASH).
Results
Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction.
Conclusion
Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.

Citations

Citations to this article as recorded by

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Diabetes & Metabolism Journal.2024; 48(3): 327. CrossRef
Improvement effect of gemigliptin on salivary gland dysfunction in exogenous methylglyoxal-injected rats
Woo Kwon Jung, Su-Bin Park, Hwa Young Yu, Junghyun Kim
Heliyon.2024; 10(8): e29362. CrossRef
Gemigliptin mitigates TGF-β-induced renal fibrosis through FGF21-mediated inhibition of the TGF-β/Smad3 signaling pathway
Jun-Kyu Byun, Gwon-Soo Jung
Biochemical and Biophysical Research Communications.2024; : 150425. CrossRef
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Xin Guo, Huolun Feng, Liyang Cai, Jiabin Zheng, Yong Li
Biomedicine & Pharmacotherapy.2024; 180: 117464. CrossRef
Gemigliptin, a DPP4 inhibitor, ameliorates nonalcoholic steatohepatitis through AMP-activated protein kinase-independent and ULK1-mediated autophagy
Youngmi Song, Hyekyung Yang, Juhee Kim, Yoonjin Lee, Sung-Ho Kim, In-Gu Do, Cheol-Young Park
Molecular Metabolism.2023; 78: 101806. CrossRef
DPP-4 Inhibitor in Type 2 Diabetes Mellitus Patient with Non-Alcoholic Fatty Liver Disease: Achieving Two Goals at Once?
Ji Cheol Bae
Endocrinology and Metabolism.2022; 37(6): 858. CrossRef

Diabetes, Obesity and Metabolism
The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis: Dinh Vinh Do, So Young Park, Giang Thi Nguyen, Dae Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2022;37(4):620-629. Published online July 22, 2022; DOI: https://doi.org/10.3803/EnM.2022.1412

6,212 View
219 Download
5 Web of Science
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Abstract PDF Supplementary Material PubReader ePub

Background
Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages.
Methods
Tamm-Horsfall protein-1 (THP-1) human monocytes were differentiated into macrophages, polarized into the inflammatory M1 phenotype with lipopolysaccharide. Lieming Xu-2 (LX-2) cells, human HSCs, were treated with conditioned media (CM) from M1 macrophages, with or without recombinant irisin. HSCs responses to CM from M1 macrophages were evaluated regarding activation, proliferation, wound healing, trans-well migration, contractility, and related signaling pathway.
Results
CM from M1 macrophages significantly promoted HSC proliferation, wound healing, transwell migration, and contractility, but not activation of HSCs. Irisin co-treatment attenuated these responses of HSCs to CM. However, CM and irisin treatment did not induce any changes in HSC activation. Further, irisin co-treatment alleviated CM-induced increase of phopho-protein kinase B (pAKT), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1).
Conclusion
These findings suggested that irisin may play a protective role in the pathogenesis of liver fibrosis, especially when working in the crosstalk between HSCs and macrophages.

Citations

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Biomedicine & Pharmacotherapy.2023; 161: 114472. CrossRef
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Yueming Zhang, Linxian Zhao, Huan Gao, Jinghui Zhai, Yanqing Song
Biomedicine & Pharmacotherapy.2023; 166: 115347. CrossRef
The effect of sarcopenia and serum myokines on prognosis and survival in cirrhotic patients: a multicenter cross-sectional study
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European Journal of Gastroenterology & Hepatology.2022;[Epub] CrossRef

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