TRPV1: A Potential Therapeutic Target in Type 2 Diabetes and Comorbidities?

TY - JOUR

T1 - TRPV1

T2 - A Potential Therapeutic Target in Type 2 Diabetes and Comorbidities?

AU - Gram, Dorte X

AU - Holst, Jens J

AU - Szallasi, Arpad

N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.

PY - 2017/11

Y1 - 2017/11

N2 - With an estimated 422 million affected patients worldwide in 2016, type 2 diabetes (T2D) has reached pandemic proportions and represents a major unmet medical need. T2D is a polygenic disease with a chronic, low-grade inflammatory component. Second-generation transient receptor potential vanilloid-1 (TRPV1) antagonists are potent anti-inflammatory agents with proven clinical safety. In rodent models of T2D, TRPV1 blockade was shown to halt disease progression and improve glucose metabolism. Thus, we propose that TRPV1 antagonists merit further study as novel therapeutic approaches to potentially treat T2D and its comorbidities. T2D is being increasingly recognized as a disease with a chronic, low-grade inflammatory component; in preclinical models, elimination of this inflammatory response improves glucose homeostasis and halts disease progression. T2D is a heterogeneous disease, so a ‘one-size-fits-all’ approach in drug development may not be feasible (elicits the need for personalized medicine). Novel antidiabetic agents that not only return blood glucose to near normal levels but also treat comorbidities such as obesity and hyperlipidemia at the same time are needed. We posit that TRPV1 antagonists may serve as putative antidiabetic agents to treat T2D; current clinical trials are investigating this possibility.

AB - With an estimated 422 million affected patients worldwide in 2016, type 2 diabetes (T2D) has reached pandemic proportions and represents a major unmet medical need. T2D is a polygenic disease with a chronic, low-grade inflammatory component. Second-generation transient receptor potential vanilloid-1 (TRPV1) antagonists are potent anti-inflammatory agents with proven clinical safety. In rodent models of T2D, TRPV1 blockade was shown to halt disease progression and improve glucose metabolism. Thus, we propose that TRPV1 antagonists merit further study as novel therapeutic approaches to potentially treat T2D and its comorbidities. T2D is being increasingly recognized as a disease with a chronic, low-grade inflammatory component; in preclinical models, elimination of this inflammatory response improves glucose homeostasis and halts disease progression. T2D is a heterogeneous disease, so a ‘one-size-fits-all’ approach in drug development may not be feasible (elicits the need for personalized medicine). Novel antidiabetic agents that not only return blood glucose to near normal levels but also treat comorbidities such as obesity and hyperlipidemia at the same time are needed. We posit that TRPV1 antagonists may serve as putative antidiabetic agents to treat T2D; current clinical trials are investigating this possibility.

KW - Journal Article

KW - Review

U2 - 10.1016/j.molmed.2017.09.005

DO - 10.1016/j.molmed.2017.09.005

M3 - Review

C2 - 29137713

SN - 1471-4914

VL - 23

SP - 1002

EP - 1013

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

IS - 11

ER -