Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes a committed and rate-limiting step in hepatic gluconeogenesis, and its activity is tightly regulated to maintain blood glucose levels within normal limits. PEPCK activity is primarily regulated through hormonal control of gene transcription. Transcription is additionally regulated via a cAMP response unit, which includes a cAMP response element and four binding sites for CCAAT/enhancer-binding protein (C/EBP). Notably, the cAMP response unit also contains a putative response element for retinoic acid receptor-related orphan receptor α (RORα). In this paper, we characterize the effect of the RORα response element on cAMP-induced transcription. Electrophoresis mobility shift assay indicates that RORα binds this response element in a sequence-specific manner. Furthermore, luciferase reporter assays indicate that RORα interacts with C/EBP at the PEPCK promoter to synergistically enhance transcription. We also found that cAMP-induced transcription depends in part on RORα and its response element. In addition, we show that suppression of RORα by siRNA significantly decreased PEPCK transcription. Finally, we found that a RORα antagonist inhibits hepatic gluconeogenesis in an in vitro glucose production assay. Taken together, the data strongly suggest that PEPCK is a direct RORα target. These results define possible new roles for RORα in hepatic gluconeogenesis.
TX 75083-3836, U.S.A., fax 01-972-952-9435.
AbstractThis paper presents a new analytical model for pressure transient tests of water injection wells in naturally fractured reservoirs. Considering negligible flow in matrix, the dualporosity model was assumed for formulating a mathematical model that accounts for two-phase flow and saturation changes in fracture and matrix. Water saturation distributions in fracture and matrix were calculated analytically using the Buckley-Leverett equation and the empirical transfer function to account for fracture-matrix flow. Pressure equations for two-phase flow were formulated with the multi-composite modeling approach. The system of pressure equations was solved analytically in Laplace space. Calculations were carried out stepwise as the injection or falloff time proceeds.The model solutions were validated for such special cases as single-phase flow in the dual-porosity model, and twophase flow in the single-porosity model. Pressure and pressure-derivative type-curves, graphed against the injection time or the dimensionless time based on well radius, exhibited features of both fractured reservoirs and two-phase flow. The parameters in the type curves are storativity ratio, interporosity two-phase flow coefficient defined as a function of shape factor, total mobilities for matrix and fracture, and exponential recovery constant R c . R c characterizes imbibitiondominant recovery performance of matrix, and is defined as a function of permeability, porosity and capillary pressure of matrix, and shape factor.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.