In this study, we aimed to investigate the role of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), which is one of the most important regulators of Alzheimer's disease development, in islet β cell dysfunction and apoptosis. We found significantly increased expression of DYRK1A in both the hippocampus and pancreatic islets of APP/PS1 transgenic mice than in wild-type littermates. Furthermore, we observed that the overexpression of DYRK1A greatly aggravated β cell apoptosis. Most importantly, we found that DYRK1A directly interacted with insulin receptor substrate-2 (IRS2) and promoted IRS2 phosphorylation, leading to the proteasomal degradation of IRS2 and promotion of β cell dysfunction and apoptosis. These findings suggested that DYRK1A is a potential drug target in diabetes mellitus.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.exger.2019.110659 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interpreting Variants of Uncertain Significance in PCD: Abnormal Splicing Caused by a Missense Variant of DNAAF3.
Mol Genet Genomic Med
January 2025
The State Key Laboratory for Complex Severe and Rare Diseases, the State Key Sci-Tech Infrastructure for Translational Medicine, Peking Union Medical College Hospital, Beijing, China.
Background: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia. While approximately 50 genes have been identified, around 25% of PCD patients remain genetically unexplained; elucidating the pathogenicity of specific variants remains a challenge.
Methods: Whole exome sequencing (WES) and Sanger sequencing were conducted to identify potential pathogenic variants of PCD.
Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle.
Front Mol Neurosci
December 2024
State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China.
Utricle is an important vestibular sensory organ for maintaining balance. 3,3'-iminodipropionitrile (IDPN), a prototype nitrile toxin, has been reported to be neurotoxic and vestibulotoxic, and can be used to establish an damage model of vestibular dysfunction. However, the mechanism of utricular HCs damage caused by IDPN is unclear.
View Article and Find Full Text PDFElucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and / experiments.
Front Pharmacol
December 2024
West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China.
Introduction: Acute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its therapeutic potential in AP have not been thoroughly investigated.
View Article and Find Full Text PDFA supercritical oil extract of seeds ameliorates Huntington's disease-like symptoms and neuropathology: the potential role of anti-oxidant and anti-inflammatory effects.
Front Pharmacol
December 2024
Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Background: Huntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. has various pharmacologic effects such as antioxidant and anti-inflammatory activities.
View Article and Find Full Text PDFCan there be calm during a cytokine storm? Immune checkpoint pathways affecting the severity of COVID-19 disease.
Front Microbiol
December 2024
Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, Hungary.
Introduction: The COVID-19 pandemic has become a global health crisis, eliciting varying severity in infected individuals. This study aimed to explore the immune profiles between moderate and severe COVID-19 patients experiencing a cytokine storm and their association with mortality. This study highlights the role of PD-1/PD-L1 and the TIGIT/CD226/CD155/CD112 pathways in COVID-19 patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!