TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?
| Autor: | Carsten F. Gotfredsen, Ana Charrua, Dorte Xenia Gram, Anker Jon Hansen, Josefine Fribo, István Nagy, John Bondo Hansen, Arpad Szallasi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system diseases glucose tolerance TRPV1 lcsh:Medicine Inflammation Carbohydrate metabolism Article vanilloid (capsaicin) receptor TRPV1 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Glucose homeostasis Receptor Neurogenic inflammation neurogenic inflammation business.industry musculoskeletal neural and ocular physiology lcsh:R nutritional and metabolic diseases Type 2 Diabetes Mellitus Blockade 030104 developmental biology Endocrinology nervous system type-2 diabetes (T2DM) lipids (amino acids peptides and proteins) medicine.symptom business TRPV1 antagonist BCTC 030217 neurology & neurosurgery |
| Zdroj: | Medical Sciences Volume 7 Issue 8 Medical Sciences, Vol 7, Iss 8, p 82 (2019) |
| ISSN: | 2076-3271 |
| Popis: | 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&minus /&minus ) 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&minus 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|