The incidence of metabolic diseases-hypertension, diabetes, obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and atherosclerosis-is increasing annually, imposing a significant burden on both human health and the social economy. The occurrence and development of these diseases are closely related to the disruption of ion homeostasis, which is crucial for maintaining cellular functions and metabolic equilibrium. However, the specific mechanism of ion homeostasis in metabolic diseases is still unclear. This article reviews the role of ion homeostasis in the pathogenesis of metabolic diseases and assesses its potential as a therapeutic target. Furthermore, the article explores pharmacological strategies that target ion channels and transporters, including existing drugs and emerging drugs under development. Lastly, the article discusses the development direction of future therapeutic strategies, including the possibility of gene therapy targeting specific ion channels and personalized therapy using novel biomarkers. In summary, targeting ion homeostasis provides a new perspective and potential therapeutic approach for the treatment of metabolic diseases.
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http://dx.doi.org/10.1016/j.phrs.2025.107579 | DOI Listing |
Background: Juxtaglomerular (JG) cells are sensors that control blood pressure and fluid-electrolyte homeostasis. In response to a decrease in perfusion pressure or changes in the composition and/or volume of the extracellular fluid, JG cells release renin, which initiates an enzymatic cascade that culminates in the production of angiotensin II (Ang II), a potent vasoconstrictor that restores blood pressure and fluid homeostasis. In turn, Ang II exerts a negative feedback on renin release, thus preventing excess circulating renin and the development of hypertension.
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Plant Production Department, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia.
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School of Pharmacy, Anhui Medical University, Hefei, China.
The activation of acid-sensing ion channel 1a (ASIC1a) in response to extracellular acidification leads to an increase in extracellular calcium influx, thereby exacerbating the degeneration of articular chondrocytes in rheumatoid arthritis (RA). It has been suggested that the inhibition of extracellular calcium influx could potentially impede chondrocyte ferroptosis. The cystine transporter, solute carrier family 7 member 11 (SLC7A11), is recognized as a key regulator of ferroptosis.
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