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.
Subject(s)
Cyclic AMP Response Element-Binding Protein/antagonists & inhibitors , Lycoris/chemistry , Phosphoenolpyruvate Carboxykinase (GTP)/metabolism , Alkaloids , Animals , Cyclic AMP Response Element-Binding Protein/metabolism , Gluconeogenesis , Humans , Phosphorylation , TransfectionABSTRACT
BACKGROUND: Practicing healthy lifestyle behaviors is a means to prevent metabolic syndrome (MetS), but the effect of changes of various behaviors over a short period is not fully understood. The purpose of this study was to elucidate the influence of changes in 12 behaviors on the development of MetS during 1 year. METHODS AND RESULTS: Of 10,442 workers who received a periodic health checkup in a health center in Tokyo in 2008, 3,137 workers aged 30-69, without MetS, who received another health checkup in 2009 were analyzed. Smoking, amounts and frequency of alcohol drinking, sleeping, exercise, walking duration and speed, late-night dinners, bedtime snacking, breakfast, eating speed, and weight control were classified into 4 groups according to change from 2008 to 2009. To examine the influence of behavioral changes on developing MetS, multiple logistic analysis was conducted after adjustment for sex, baseline age and MetS components. Changes from healthy to unhealthy behaviors in exercise, walking duration and speed, daily drinking, and weight control were significant in developing MetS compared with maintaining healthy behaviors. Those risks were higher than keeping unhealthy behaviors. Unhealthy to healthy behavior in smoking increased the risk while healthy to unhealthy behavior in eating speed decreased the risk of developing MetS. CONCLUSIONS: To prevent developing MetS during 1 year, healthy behaviors regarding physical activity, drinking, and weight management should be maintained.
Subject(s)
Alcohol Drinking , Life Style , Metabolic Syndrome , Motor Activity , Smoking , Adult , Aged , Alcohol Drinking/adverse effects , Alcohol Drinking/physiopathology , Female , Humans , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Metabolic Syndrome/physiopathology , Middle Aged , Smoking/adverse effects , Smoking/physiopathology , TokyoABSTRACT
The p450 aromatase gene has a tissue-specific promoter that is regulated by specific transcriptional factors. In rats and humans, a cAMP response element-like sequence (CLS) and an NR5A1/NR5A2 binding sequence have been identified as cis elements in the aromatase promoter; these cis elements mediate cAMP-induced expression in the ovaries and testes. CLS is recognized by a cAMP-responsive element binding protein (CREB) as the principal component. In this study, we performed a gel shift assay to analyze the proteins that interact with the cis-element in Xenopus aromatase. An electrophpretic mobility gel shift assay (EMSA) and matrix-associated laser desorption ionization time of flight (MALDI-TOF) mass spectrometry (MS) analysis of the proteins responsible for retarding the mobility of CLS revealed that ATF4 interacted in vitro with CLS in gonadal specific aromatase promoter sequence of Xenopus embryos. Although a significant difference was observed in aromatase mRNA expression between male and female gonads, no difference in the expression of ATF4 was observed between them at stage 50. With regard to aromatase expression in the gonad of Xenopus embryos, ATF4 might act in combination with multiple transcription factors as a trans-element of CLS in place of CREB.
