Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes-related complications

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

With an estimated 425 million diabetes patients worldwide in 2019, type 2 diabetes has reached a pandemic proportion and represents a major unmet medical need. A key determinant of the development and progression of type 2 diabetes is pancreatic -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 2+ -permeable non-selective cation channel, is involved in -cell replication, insulin production and secretion. TRPV4 agonists have insulinotropic activity in pancreatic -cell lines, but the prolonged activation of TRPV4 leads to -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 type 2 diabetes model, Trpv4 agonists promote vasodilation and improve cardiovascular function, whereas 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 type 2 diabetes. In this review, we intend to summarize the latest findings regarding the role of TRPV4 in diabetes as

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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