title: Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119.
abstract: G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes.
authors.affiliation: College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam, 534-729, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Park
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon, 406-840, South Korea.
authors.forename: Eung-Hwi
authors.initials: EH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Hanyang University, Ansan, Kyeonggi, 426-791, Republic of Korea.
authors.forename: Chul-Young
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon, 406-840, South Korea.
authors.forename: Mi-Hwi
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon, 406-840, South Korea.
authors.forename: Jin-Seung
authors.initials: JS
authors.lastname: Choung
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon, 406-840, South Korea.|Gachon Medical Research Institute, Gil Hospital, Incheon, South Korea.
authors.forename: Yoon-Sin
authors.initials: YS
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam, 534-729, Republic of Korea.
authors.forename: Hong-Sub
authors.initials: HS
authors.lastname: Moon
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon, 406-840, South Korea.|Gachon Medical Research Institute, Gil Hospital, Incheon, South Korea.|College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon, 406-840, South Korea.
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
mesh_terms: D029969:Angelica / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007739:L Cells; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C519854:GPR119 protein, human; C532423:GPR119 protein, rat; C516207:Gpr119 protein, mouse; D010936:Plant Extracts; D043562:Receptors, G-Protein-Coupled