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

• Published in: The FASEB journal Vol. 31; no. 6; pp. 2603 - 2611
• Main Authors: Li, Ying, Zheng, Xuemin, Yi, Xiulin, Liu, Changxiao, Kong, Dexin, Zhang, Jianning, Gong, Min
• Format: Journal Article
• Language: English
• Published: United States 01.06.2017
• Subjects: Amino Acids; Animals; Blood Glucose - metabolism; Chromium; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Type 2 - drug therapy; Flavonoids - pharmacology; GLP‐1 receptor; Glucagon-Like Peptide-1 Receptor - agonists; glucose tolerance test; Humans; Insulin - metabolism; insulin secretagogue; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Male; Mice; Mice, Knockout; Nicotinic Acids; oral agonist; Rats, Wistar; Rats, Zucker; insulin secretagogue; glucose tolerance test; oral agonist; GLP-1 receptor
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201601339R

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. FASEB J. 31, 2603–2611 (2017). www.fasebj.org