title: The Anthocyanin Delphinidin 3-Rutinoside Stimulates Glucagon-Like Peptide-1 Secretion in Murine GLUTag Cell Line via the Ca2+/Calmodulin-Dependent Kinase II Pathway.
abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L-cells. Although several nutrients induce GLP-1 secretion, there is little evidence to suggest that non-nutritive compounds directly increase GLP-1 secretion. Here, we hypothesized that anthocyanins induce GLP-1 secretion and thereby significantly contribute to the prevention and treatment of diabetes. Delphinidin 3-rutinoside (D3R) was shown to increase GLP-1 secretion in GLUTag L cells. The results suggested that three hydroxyl or two methoxyl moieties on the aromatic ring are essential for the stimulation of GLP-1 secretion. Notably, the rutinose moiety was shown to be a potent enhancer of GLP-1 secretion, but only in conjunction with three hydroxyl moieties on the aromatic ring (D3R). Receptor antagonist studies revealed that D3R-stimulates GLP-1 secretion involving inositol 1,4,5-trisphosphate receptor-mediated intracellular Ca2+ mobilization. Treatment of GLUTag cells with a Ca2+/calmodulin-dependent kinaseII (CaMKII) inhibitor (KN-93) abolished D3R-stimulated GLP-1 secretion. In addition, treatment of GLUTag cells with D3R resulted in activation of CaMKII. Pre-treatment of cells with a G protein-coupled receptor (GPR) 40/120 antagonist (GW1100) also significantly decreased D3R-stimulated GLP-1 secretion. These observations suggest that D3R stimulates GLP-1 secretion in GLUTag cells, and that stimulation of GLP-1 secretion by D3R is mediated via Ca2+-CaMKII pathway, which may possibly be mediated by GPR40/120. These findings provide a possible molecular mechanism of GLP-1 secretion in intestinal L-cells mediated by foods or drugs and demonstrate a novel biological function of anthocyanins in regards to GLP-1 secretion.
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Tani
authors.affiliation: Department of Food Science and Technology, Minami-Kyushu University, Miyazaki, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Terahara
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000872:Anthocyanins; D001565:Benzoates; C515631:GW1100; D011743:Pyrimidines; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2