ArticleThe Journal of endocrinology2019
Endothelial adenosine kinase deficiency ameliorates diet-induced insulin resistance.
Article in The Journal of endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Single-cell transcriptome analysis highlights a critical role of ATG5 for endothelial cells in diabetic nephropathy.Human cell · 2025Article
- Adenosine kinase inhibition protects mice from abdominal aortic aneurysm via epigenetic modulation of VSMC inflammation.Cardiovascular research · 2024Article
- Endothelial cell-derived stem cell factor promotes lipid accumulation through c-Kit-mediated increase of lipogenic enzymes in brown adipocytes.Nature communications · 2023Article
- Hepatocyte Adenosine Kinase Promotes Excessive Fat Deposition and Liver Inflammation.Gastroenterology · 2023Article
- Article
- PPARγ alleviates peritoneal fibrosis progression along with promoting GLUT1 expression and suppressing peritoneal mesothelial cell proliferation.Molecular and cellular biochemistry · 2022Article
- Endothelial AMPKα1/PRKAA1 exacerbates inflammation in HFD-fed mice.British journal of pharmacology · 2022Article
- Diabetes and hypertension: Pivotal involvement of purinergic signaling.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Deficiency of Myeloid Pfkfb3 Protects Mice From Lung Edema and Cardiac Dysfunction in LPS-Induced Endotoxemia.Frontiers in cardiovascular medicine · 2021Article
- Pharmacological Tuning of Adenosine Signal Nuances Underlying Heart Failure With Preserved Ejection Fraction.Frontiers in pharmacology · 2021Review
- Adenosine kinase inhibition enhances microvascular dilator function and improves left ventricle diastolic dysfunction.Microcirculation (New York, N.Y. : 1994) · 2020Article
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Insulin resistance-related disorders are associated with endothelial dysfunction. Accumulating evidence has suggested a role for adenosine signaling in the regulation of endothelial function. Here, we identified a crucial role of endothelial adenosine kinase (ADK) in the regulation of insulin resistance. Feeding mice with a high-fat diet (HFD) markedly enhanced the expression of endothelial Adk. Ablation of endothelial Adk in HFD-fed mice improved glucose tolerance and insulin sensitivity and decreased hepatic steatosis, adipose inflammation and adiposity, which were associated with improved arteriole vasodilation, decreased inflammation and increased adipose angiogenesis. Mechanistically, ADK inhibition or knockdown in human umbilical vein endothelial cells (HUVECs) elevated intracellular adenosine level and increased endothelial nitric oxide synthase (NOS3) activity, resulting in an increase in nitric oxide (NO) production. Antagonism of adenosine receptor A2b abolished ADK-knockdown-enhanced NOS3 expression in HUVECs. Additionally, increased phosphorylation of NOS3 in ADK-knockdown HUVECs was regulated by an adenosine receptor-independent mechanism. These data suggest that Adk-deficiency-elevated intracellular adenosine in endothelial cells ameliorates diet-induced insulin resistance and metabolic disorders, and this is associated with an enhancement of NO production caused by increased NOS3 expression and activation. Therefore, ADK is a potential target for the prevention and treatment of metabolic disorders associated with insulin resistance.
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