title: Qing-Hua Granule induces GLP-1 secretion via bitter taste receptor in db/db mice.
abstract: Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks. GLP-1 secretion was evaluated. The bitter receptor signaling pathway, which regulates GLP-1 secretion, including TAS2R5 (a subtype of TAS2R), α-gustducin (Gαgust), 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase beta-2 (PLCβ2), transient receptor potential cation channel subfamily M member 5 (TRPM5), was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). The biochemical observations of ileum and pancreas tissue were detected histopathologically. Acquity Ultra Performance LCTM - Micromass ZQ 2000 (UPLC-MS) was used for the phytochemical analysis. QHG exhibited significant and dose-dependent effect on GLP-1 secretion in db/db mice, along with significant up-regulation of TAS2R5 mRNA level and activation of TAS2R pathway (p<0.05). In addition, QHG improved the histopathological structure of ileum and pancreatic tissue. Seventeen compounds were identified in QHG. In conclusion, QHG induces GLP-1 secretion in db/db mice, most likely through the bitter taste receptor pathway.
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Hou
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: leecj123@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Tao
authors.affiliation: Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D001786:Blood Glucose; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D010179:Pancreas / Q000187:drug effects; D011208:Powders; D015398:Signal Transduction / Q000187:drug effects; D013649:Taste; D013650:Taste Buds / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D011208:Powders; C542794:gegenqinlian; D052216:Glucagon-Like Peptide 1
keywords: Glucagon-like peptide-1; Qing-Hua granule; Traditional Chinese Medicine