title: Two Alkaloids from Bulbs of Lycoris sanguinea MAXIM.Suppress PEPCK Expression by Inhibiting the Phosphorylation of CREB.
abstract: In the fasting state, gluconeogenesis is upregulated by glucagon. Glucagon stimulates cyclic adenosine monophosphate production, which induces the expression of key enzymes for gluconeogenesis, such as cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), which are involved in gluconeogenesis through the protein kinase A/cAMP response element-binding protein (CREB) pathway. Using a luciferase reporter gene assay, a methanol extract of the bulbs of Lycoris sanguinea MAXIM.var. kiushiana Makino was found to suppress cAMP-enhanced PEPCK-C promoter activity. In addition, two alkaloids, lycoricidine and lycoricidinol, in the extract were identified as active constituents. In forskolin-stimulated human hepatoma cells, these alkaloids suppressed the expression of a reporter gene under the control of cAMP response element and also prevented increases in the endogenous levels of phosphorylated CREB and PEPCK mRNA expression. These results suggest that lycoricidine and lycoricidinol suppress PEPCK-C expression by inhibiting the phosphorylation of CREB and may thus have the potential to prevent excessive gluconeogenesis in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan. yun@toyaku.ac.jp.
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Yun
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tajima
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Umemura
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Nakano
authors.affiliation: The Kochi Prefectural Makino Botanical Garden, Kochi City, Kochi Prefecture, 781-8125, Japan.|School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Park
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000470:Alkaloids; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005943:Gluconeogenesis; D006801:Humans; D031426:Lycoris / Q000737:chemistry*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D010766:Phosphorylation; D014162:Transfection
chemical_list: D000470:Alkaloids; D017362:Cyclic AMP Response Element-Binding Protein; D010729:Phosphoenolpyruvate Carboxykinase (GTP)
keywords: PEPCK; cAMP/PKA/CREB pathway; gluconeogenesis; lycoricidine; lycoricidinol