Therapeutic significance of peroxisome proliferator-activated receptor modulators in diabetes.
Peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms, identified and encoded by different genes: PPARalpha, PPARdelta and PPARgamma. Each subtype of PPAR appears to be differently expressed in a tissue-specific manner due to its binding to a specific consensus DNA sequence of peroxisome proliferator response elements (PPREs). PPARalpha plays a significant role in the regulation of nutrient metabolism, including fatty acid oxidation, gluconeogenesis and amino acid metabolism. PPARdelta is expressed ubiquitously and has been found to be effective in controlling dyslipidemia and cardiovascular diseases, while PPARgamma isotype is mainly expressed in adipose tissue where it stimulates adipogenesis and lipogenesis. Thus PPARs have emerged as potential molecular targets for the design and synthesis of a different class of compounds, considering the conformation of receptors for the treatment of human metabolic disorders. This review concerns the therapeutic importance of PPARs in diabetes drug development.
Ram
Vishnu Ji
VJ
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India. vjiram@yahoo.com
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000096:biosynthesis / Q000502:physiology; D045162:Thiazolidinediones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists* / Q000096:biosynthesis / Q000502:physiology
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D008024:Ligands; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors