Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity

Abstract

Diabetes mellitus and obesity, which is a major risk factor in the development of type 2 diabetes mellitus, have reached epidemic proportions worldwide including the United States. The current statistics and forecasts, both short- and long-term, are alarming and predict severe problems in the near future. Therefore, there is a race for developing new compounds, discovering new receptors or finding alternative solutions to prevent and/or treat the symptoms and complications related to obesity and diabetes mellitus. It is well demonstrated that members of the transient receptor potential (TRP) superfamily play a crucial role in a variety of biological functions both in health and disease. In the recent years, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) were shown to have beneficial effects on whole body metabolism including glucose homeostasis. TRPV1 and TRPA1 have been associated with control of weight, pancreatic function, hormone secretion, thermogenesis and neuronal function; which suggest a potential therapeutic value of these channels. This review summarizes recent findings regarding TRPV1 and TRPA1 in association with whole body metabolism with emphasis on obese and diabetic conditions.

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

“…The studies determined that liver-related neurons receive transient receptor potential vanilloid type 1 (TRPV1) containing inputs. TRPV1 is a non-selective cation channel and has been linked to the development and progression of type 1 diabetes mellitus and T2D (134), and recent reviews have discussed its role in diabetes mellitus and obesity in further detail (135, 136). The TRPV1-dependent excitation of liver-related PVN neurons was diminished in a hyperglycemic, insulin-deficient mouse model.…”

Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2

“…The role of TRPV1 in these settings, particularly in endothelial dysfunction in obesity and diabetes, has recently been demonstrated (Lee et al . ) and reviewed (Derbenev & Zsombok ). Nevertheless, TRPV1‐dependent renovascular changes in these pathophysiological conditions need further investigations.…”

Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus

“…Accumulating evidence indicates that TRPV1 plays an essential role in the underlying processes of heart failure, indicating that the modulation of TRPV1 may be a potential target for CHF treatment in diabetes [2,28]. Indeed, defects of TRPV1 have been associated with the occurrence of heart failure in type 1 and 2 diabetes mellitus due to their effects on ROS production, Ca 2+ transients, eNOS activity, adiponectin and leptin signaling control, the modulation of neuronal activity, microcirculatory vasodilation, and the regulation of myocardial blood flow [12,[29][30][31][32].…”

“…Recently, Issa reported that increased expression of transient receptor potential vanilloid 1 (TRPV1) protein is observed in rats with angiotensin II (Ang II)-dependent malignant hypertension, which indicates that TRPV1 may be an important contributing factor to these effects of Ang II [11]. Moreover, the role of the TRPV1 channel in the regulation of cardiovascular dysfunction in diabetes has been established [2]. Zheng demonstrated impaired TRPV1 activity and deficient levels of primary downstream transmitters, such as calcitonin gene related peptide (CGRP) and substance P (SP), in the hearts of diabetic mice and patients [12].…”

“…improving diabetes and preventing further cardiovascular complications include blood sugar maintenance, lifestyle changes, and pharmacological interventions [2]. However, the pathogenesis of cardiovascular complications and the optimum treatments for diabetic patients remain unclear.…”