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Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119

Title
Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119
Author
김철영
Keywords
PROTEIN-COUPLED RECEPTOR; GLYCEMIC CONTROL; TYPE-2; AGONISTS; FURANOCOUMARINS; PATHOGENESIS; RELEASE; OBESITY; AGENTS; ROOTS
Issue Date
2016-07
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v. 11, No. 7, Article no. e0158796
Abstract
G protein-coupled receptor (GPR) 119 is expressed in pancreatic beta-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.
URI
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158796http://hdl.handle.net/20.500.11754/65638
ISSN
1932-6203
DOI
10.1371/journal.pone.0158796
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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