PMID- 31344877
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2076-3271 (Electronic)
IS  - 2076-3271 (Linking)
VI  - 7
IP  - 8
DP  - 2019 Jul 24
TI  - TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose 
      Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?
LID - 10.3390/medsci7080082 [doi]
LID - 82
AB  - With a global prevalence among adults over 18 years of age approaching 9%, Type 2 
      diabetes mellitus (T2DM) has reached pandemic proportions and represents a major 
      unmet medical need. To date, no disease modifying treatment is available for T2DM 
      patients. Accumulating evidence suggest that the sensory nervous system is 
      involved in the progression of T2DM by maintaining low-grade inflammation via the 
      vanilloid (capsaicin) receptor, Transient Receptor Potential Vanilloid-1 (TRPV1). 
      In this study, we tested the hypothesis that TRPV1 is directly involved in 
      glucose homeostasis in rodents. TRPV1 receptor knockout mice (Trpv1(-/-)) and 
      their wild-type littermates were kept on high-fat diet for 15 weeks. Moreover, 
      Zucker obese rats were given the small molecule TRPV1 antagonist, 
      N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide 
      (BCTC), per os twice-a-day or vehicle for eight days. Oral glucose tolerance and 
      glucose-stimulated insulin secretion was improved by both genetic inactivation 
      (Trpv1(-/-) mice) and pharmacological blockade (BCTC) of TRPV1. In the obese rat, 
      the improved glucose tolerance was accompanied by a reduction in inflammatory 
      markers in the mesenteric fat, suggesting that blockade of low-grade inflammation 
      contributes to the positive effect of TRPV1 antagonism on glucose metabolism. We 
      propose that TRPV1 could be a promising therapeutic target in T2DM by improving 
      glucose intolerance and correcting dysfunctional insulin secretion.
FAU - Gram, Dorte X
AU  - Gram DX
AD  - PILA Pharma, 211 21 Malmo, Sweden. dxg@pilapharma.com.
AD  - Former Employee, Research & Development, Novo Nordisk A/S, 2760 Malov, Denmark. 
      dxg@pilapharma.com.
FAU - Fribo, Josefine
AU  - Fribo J
AD  - Former Employee, Research & Development, Novo Nordisk A/S, 2760 Malov, Denmark.
FAU - Nagy, Istvan
AU  - Nagy I
AUID- ORCID: 0000-0003-3475-6108
AD  - Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, 
      London SW7 2AZ, UK.
FAU - Gotfredsen, Carsten
AU  - Gotfredsen C
AD  - Former Employee, Research & Development, Novo Nordisk A/S, 2760 Malov, Denmark.
FAU - Charrua, Ana
AU  - Charrua A
AUID- ORCID: 0000-0002-7717-7790
AD  - Institute of Histology and Embryology, Faculty of Medicine, University of Porto, 
      Alameda Prof Hernani Monteiro, 4099-002 Porto, Portugal.
FAU - Hansen, John B
AU  - Hansen JB
AD  - Former Employee, Research & Development, Novo Nordisk A/S, 2760 Malov, Denmark.
AD  - Concit Pharma APS, 4450 Jyderup, Denmark.
FAU - Hansen, Anker J
AU  - Hansen AJ
AD  - Former Employee, Research & Development, Novo Nordisk A/S, 2760 Malov, Denmark.
FAU - Szallasi, Arpad
AU  - Szallasi A
AD  - 1st Department of Pathology and Experimental Cancer Research, Semmelweis 
      University, 1085 Budapest, Hungary.
LA  - eng
PT  - Journal Article
DEP - 20190724
PL  - Switzerland
TA  - Med Sci (Basel)
JT  - Medical sciences (Basel, Switzerland)
JID - 101629322
PMC - PMC6722836
OTO - NOTNLM
OT  - TRPV1 antagonist BCTC
OT  - glucose tolerance
OT  - neurogenic inflammation
OT  - type-2 diabetes (T2DM)
OT  - vanilloid (capsaicin) receptor TRPV1
COIS- Dorte X. Gram is the founder, shareholder and CEO of Pila Pharma that holds 
      several patents on the use of TRPV1 antagonists in diabetes and obesity. Arpad 
      Szallasi is a scientific advisor to Pila Pharma. All other authors report no 
      potential conflicts of interest.
EDAT- 2019/07/28 06:00
MHDA- 2019/07/28 06:01
PMCR- 2019/07/24
CRDT- 2019/07/27 06:00
PHST- 2019/05/31 00:00 [received]
PHST- 2019/07/03 00:00 [revised]
PHST- 2019/07/10 00:00 [accepted]
PHST- 2019/07/27 06:00 [entrez]
PHST- 2019/07/28 06:00 [pubmed]
PHST- 2019/07/28 06:01 [medline]
PHST- 2019/07/24 00:00 [pmc-release]
AID - medsci7080082 [pii]
AID - medsci-07-00082 [pii]
AID - 10.3390/medsci7080082 [doi]
PST - epublish
SO  - Med Sci (Basel). 2019 Jul 24;7(8):82. doi: 10.3390/medsci7080082.