Myricetin: a potent approach for the treatment of type 2 diabetes as a natural class B GPCR agonist

被引：62
作者：
Li, Ying [1 ]
Zheng, Xuemin [3 ]
Yi, Xiulin [3 ]
Liu, Changxiao [3 ]
Kong, Dexin [2 ]
Zhang, Jianning [1 ]
Gong, Min [2 ,4 ]
机构：
[1] Tianjin Med Univ, Gen Hosp, Tianjin Neurol Inst, Tianjin, Peoples R China
[2] Tianjin Med Univ, Dept Pharm, Tianjin 300070, Peoples R China
[3] Tianjin Inst Pharmaceut Res, State Key Lab Drug Delivery Technol & Pharmacokin, Tianjin, Peoples R China
[4] Univ Oxford, Dept Oncol, Oxford, England
来源：
FASEB JOURNAL | 2017年 / 31卷 / 06期
关键词：
GLP-1; receptor; oral agonist; insulin secretagogue; glucose tolerance test; GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; CARDIOVASCULAR-DISEASE; CELL-PROLIFERATION; METABOLIC SYNDROME; RAT ADIPOCYTES; BETA-CELLS; MOLECULE; GLP-1; DIFFERENTIATION;
D O I：
10.1096/fj.201601339R
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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-termoral 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.
引用
收藏
页码：2603 / 2611
页数：9
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