Transient Receptor Potential Vanilloid 1 Activation Enhances Gut Glucagon-Like Peptide-1 Secretion and Improves Glucose Homeostasis

Abstract

Type 2 diabetes mellitus (T2DM) is rapidly prevailing as a serious global health problem. Current treatments for T2DM may cause side effects, thus highlighting the need for newer and safer therapies. We tested the hypothesis that dietary capsaicin regulates glucose homeostasis through the activation of transient receptor potential vanilloid 1 (TRPV1)-mediated glucagon-like peptide-1 (GLP-1) secretion in the intestinal cells and tissues. Wild-type (WT) and TRPV1 knockout (TRPV1−/−) mice were fed dietary capsaicin for 24 weeks. TRPV1 was localized in secretin tumor cell-1 (STC-1) cells and ileum. Capsaicin stimulated GLP-1 secretion from STC-1 cells in a calcium-dependent manner through TRPV1 activation. Acute capsaicin administration by gastric gavage increased GLP-1 and insulin secretion in vivo in WT but not in TRPV1−/− mice. Furthermore, chronic dietary capsaicin not only improved glucose tolerance and increased insulin levels but also lowered daily blood glucose profiles and increased plasma GLP-1 levels in WT mice. However, this effect was absent in TRPV1−/− mice. In db/db mice, TRPV1 activation by dietary capsaicin ameliorated abnormal glucose homeostasis and increased GLP-1 levels in the plasma and ileum. The present findings suggest that TRPV1 activation–stimulated GLP-1 secretion could be a promising approach for the intervention of diabetes.

Regulation of GPR119 receptor activity with endocannabinoid-like lipids

“…5), a result that can be rationalized by cannabinoid receptor activation counteracting the GPR119 agonist-induced rise in cAMP levels. The TRPV1 antagonist SB-366791 lowered both basal and OEA-induced GLP-1 secretion to a similar extent, confirming previous observations on the role of TRPV1 in the regulation of GLP-1 secretion (34). The PPAR ligands tesaglitazar and GW-9662 had no impact on basal or OEA-induced GLP-1 secretion.…”

“…Recently, the TRPV1 channel has been implicated in the regulation of GLP-1 secretion, and the TRPV1 agonist capsaicin has been reported to trigger GLP-1 secretion in STC-1 cells (34). In GLUTag cells, we did not see a significant modulation of GLP-1 secretion with arvanil under basal conditions, whereas the selective TRPV1 antagonist SB-366791 inhibited basal GLP-1 secretion.…”

Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1–Mediated Protein Kinase A/Uncoupling Protein 2 Pathway

“…38 Our previous studies showed that TRPV1 activation by dietary capsaicin alleviates metabolic disorders and attenuates aortic atherosclerosis as well as hypertension. 21,33,39,40 In this study, we further demonstrated that chronic dietary capsaicin supplementation ameliorated HFDinduced endothelial dysfunction in the coronary arteries and prolonged the lifespan of ApoE −/− receiving HFD. Moreover, we showed that the activation of TRPV1 by dietary capsaicin increased UCP2 expression and reduced ROS generation in ECs and arteries, and that these effects were associated with −/− mice fed with HFD or HC.…”

Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress-induced podocyte apoptosis in diabetic nephropathy

“…25 After an overnight fast, GTT or ITT were performed by intraperitoneal injection of glucose (2 g/kg) or insulin (0.75 U/kg) in sterile saline, respectively. Blood glucose was measured at 0, 15, 30, 60, 90 and 120 min by an OneTouch Ultra blood glucose meter (OMRON, Kyoto, Japan).…”