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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, COS Cells, Cercopithecus aethiops, Genes, Reporter, Glyburide, Hep G2 Cells, Humans, Hypoglycemic Agents, Models, Molecular, Molecular Dynamics Simulation, Protein Conformation, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Sulfonylurea Compounds, Transcriptional Activation.
user
Do antidiabetic sulfonylureas modulate farnesoid X receptor activation and target gene transcription? Context: The sulfonylureas glibenclamide and glimepiride are oral antidiabetic drugs that stimulate insulin secretion by closing pancreatic ATP-dependent potassium channels. The farnesoid X receptor (FXR) is a ligand-activated transcription factor that regulates the expression of several target genes involved in bile acid metabolism and lipid and glucose homeostasis. In this study we investigated the potential effects of sulfonylureas on the signaling of FXR using a reporter-gene assay, real-time qPCR and computational methods such as molecular docking and molecular dynamic simulations. We demonstrate that glibenclamide and glimepiride modulate FXR activation in a reporter-gene assay and induce FXR target genes in HepG2 cells. Within the docking experiments and molecular dynamics simulation, we found glibenclamide interacting with the ligand-binding domain of FXR and with helix 12.
assistant
Glibenclamide and glimepiride are potential ligands of FXR and modulate activation and signaling. Final Decision: yes