Enhanced insulin secretion and sensitization in diabetic mice on chronic treatment with a transient receptor potential vanilloid 1 antagonist

Life Sciences ◽  
2011 ◽  
Vol 88 (11-12) ◽  
pp. 559-563 ◽  
Author(s):  
Hirotsugu Tanaka ◽  
Akiyoshi Shimaya ◽  
Tetsuo Kiso ◽  
Takahiro Kuramochi ◽  
Teruhiko Shimokawa ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Chronic Treatment ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Diabetic Mice ◽  
Transient Receptor

scholarly journals TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?

2019 ◽  
Vol 7 (8) ◽  
pp. 82 ◽  
Author(s):  
Dorte X. Gram ◽  
Josefine Fribo ◽  
Istvan Nagy ◽  
Carsten Gotfredsen ◽  
Ana Charrua ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Oral Glucose ◽  
Transient Receptor Potential Vanilloid ◽  
Low Grade ◽  
Oral Glucose Tolerance ◽  
Transient Receptor ◽  
Low Grade Inflammation

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.

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