Author : Jacob E. Friedman
Published in : Elsevier
ISBN No. : 978-0-444-51158-4
File Type : pdf
File Size : 5 mb
Language : English
Description
The activation of nuclear receptors and DNA binding proteins serves as a final target for hormones and intracellular signaling pathways underlying many important physiological and biochemical pathways. Over the last 5–10 years, a new era of research has begun, arising from the application of molecular biology to the field of transcriptional regulation of metabolism and obesity. In addition, the application of transgenic and gene knockout technology to uncover the role of these transcription factors, and their potential application for therapeutic intervention, has led to new insights and broader understanding of the clinical relevance of these proteins in metabolic research. Efforts to understand the mechanisms that underlie susceptibility to diabetes have primarily focused on structure–function of genes encoding receptors, enzymes, and transporters. More recently, the study of specific transcription factors has provided a new basis for understanding the integrated mechanisms of diabetes and metabolism. A powerful example of this integration is the discovery in 1996 of mutations in genes encoding transcription factors HNF-1a and HNF-4a (hepatic nuclear factor 4a/1a) as underlying causes of inherited MODY (maturity onset diabetes of youth). Another excellent example is the discovery of the thiazolidinedione (TZD) receptor class of drugs, which bind to PPARg, a nuclear hormone receptor. The uncovering of associations between transcription factors and the pathophysiology of diabetes is an exciting new field with many recent new findings. Thus, understanding how transcription factors regulate fundamental metabolic processes should have broad appeal to an array of basic and clinical scientists.
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