With an estimated 425 million diabetic patients worldwide in 2019, type 2 diabetes (T2D) has reached a pandemic proportion and represents a major unmet medical need. A key determinant of the development and progression of T2D is pancreatic beta-cell dysfunction, including the loss of cell mass, the impairment of insulin biosynthesis, and inadequate exocytosis. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), a Ca -permeable nonselective cation channel, is involved in beta-cell replication, insulin production and secretion. TRPV4 agonists have insulinotropic activity in pancreatic beta-cell lines, but the prolonged activation of TRPV4 leads to beta-cell dysfunction and death. In addition, TRPV4 is involved in a wide variety of pathophysiological activities and has been reported to play an important role in diabetes-related complications such as obesity, cardiovascular diseases, diabetic retinopathy, nephropathy, and neuropathy. In a rodent T2D model, Trpv4 agonists promote vasodilation and improve cardiovascular function, while Trpv4 antagonists reduce high-fat diet-induced obesity, insulin resistance, diabetic nephropathy, retinopathy, and neuropathy. These findings raise interest in using TRPV4 as a therapeutic target for T2D. In this review, we intend to summarize the latest findings regarding the role of TRPV4 in diabetes as well as diabetes-related conditions and to evaluate its potential as a therapeutic target for diabetes and diabetes-related diseases.This article is protected by copyright. All rights reserved.
December 9, 2019
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