title: Myricetin: a potent approach for the treatment of type 2 diabetes as a natural class B GPCR agonist.
abstract: The physiologic properties of glucagon-like peptide 1 (GLP-1) make it a potent candidate drug target in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 is capable of regulating the blood glucose level by insulin secretion after administration of oral glucose. The advantages of GLP-1 for the avoidance of hypoglycemia and the control of body weight are attractive despite its poor stability. The clinical efficacies of long-acting GLP-1 derivatives strongly support discovery pursuits aimed at identifying and developing orally active, small-molecule GLP-1 receptor (GLP-1R) agonists. The purpose of this study was to identify and characterize a novel oral agonist of GLP-1R (i.e., myricetin). The insulinotropic characterization of myricetin was performed in isolated islets and in Wistar rats. Long-term oral administration of myricetin demonstrated glucoregulatory activity. The data in this study suggest that myricetin might be a potential drug candidate for the treatment of T2DM as a GLP-1R agonist. Further structural modifications on myricetin might improve its pharmacology and pharmacokinetics.-Li, Y., Zheng, X., Yi, X., Liu, C., Kong, D., Zhang, J., Gong, M. Myricetin: a potent approach for the treatment of type 2 diabetes as a natural class B GPCR agonist.
authors.affiliation: Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China.
authors.forename: Xiulin
authors.initials: X
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China.
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Kong
authors.affiliation: Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; kahongmg@hotmail.com.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Tianjin Medical University, Tianjin, China; gongmin@tmu.edu.cn.|Department of Oncology, University of Oxford, Oxford, United Kingdom.
authors.forename: Min
authors.initials: M
authors.lastname: Gong
mesh_terms: D000596:Amino Acids; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002857:Chromium; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009539:Nicotinic Acids; D017208:Rats, Wistar; D011924:Rats, Zucker; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D005419:Flavonoids; D007328:Insulin; D009539:Nicotinic Acids; C015240:glucose tolerance factor; D002857:Chromium; C040015:myricetin; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: GLP-1 receptor; glucose tolerance test; insulin secretagogue; oral agonist