title: Low-molecular fraction of wheat protein hydrolysate stimulates glucagon-like peptide-1 secretion in an enteroendocrine L cell line and improves glucose tolerance in rats.
abstract: The incretin hormone glucagon-like peptide-1 (GLP-1) is secreted by enteroendocrine L cells. Stimulating endogenous GLP-1 secretion by dietary factors is a promising strategy to increase GLP-1 action. Several studies have examined the specific physiological function of wheat protein hydrolysate. Some reports suggested that intake of wheat protein ameliorates hyperglycemia. We hypothesized that wheat protein hydrolysate reduces blood glucose concentration via stimulation of GLP-1 secretion. In this study, we investigated whether wheat protein hydrolysate stimulates GLP-1 secretion and its molecular mechanism in an enteroendocrine L cell line (GLUTag cells), and we examined the effect on glucose tolerance via stimulation of GLP-1 secretion followed by induction of insulin secretion in rats. The low-molecular fraction of wheat protein hydrolysate (LWP) significantly increased GLP-1 secretion, whereas the high-molecular fraction did not. This increase was found to involve activation of the Ca2+/calmodulin-dependent kinase II pathway mediated by G protein-coupled receptor family C group 6 subtype A. Moreover, preadministration of LWP ameliorated hyperglycemia via the stimulation of GLP-1 secretion followed by induction of insulin secretion in rats. Furthermore, this LWP-induced glucose-lowering effect was significantly attenuated by the administration of a GLP-1 receptor antagonist. These results demonstrate that LWP significantly increased GLP-1 secretion through activation of the Ca2+/calmodulin-dependent kinase II pathway mediated by G protein-coupled receptor family C group 6 subtype A in GLUTag cells. Moreover, preadministration of LWP ameliorated hyperglycemia via the stimulation of GLP-1 secretion followed by induction of insulin secretion in rats.
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 487-8501, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 487-8501, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 487-8501, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Tani
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 487-8501, Japan. Electronic address: tsudat@isc.chubu.ac.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002460:Cell Line; D019858:Enteroendocrine Cells / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D018149:Glucose Intolerance / Q000097:blood / Q000517:prevention & control; D006943:Hyperglycemia / Q000097:blood* / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008970:Molecular Weight; D011492:Protein Hydrolysates / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D014908:Triticum / Q000737:chemistry*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011492:Protein Hydrolysates; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Ca(2+)/calmodulin-dependent kinase II; Glucagon-like peptide-1; Intestinal L cells; Rats; Wheat protein hydrolysate