title: Discovery of Novel Anti-Diabetic Drugs by Targeting Lipid Metabolism.
abstract: Accumulation of toxic lipids is the most common etiology of insulin resistance in type 2 diabetes and associated metabolic disorders such as obesity and non-alcoholic fatty liver disease. Understanding of the underlying mechanisms has revealed various opportunities to target key regulators in lipid metabolic pathways for the treatment of metabolic diseases. Here, we review the discovery and development of potential anti-diabetic drugs with primary effects on cellular targets leading to reductions of intracellular lipids in key organs. We will particularly focus on AMPK, SIRT1, PGC-1α, SREBP-1c, ChREBP, ACC, PPARs and HSPs which either stimulate in fatty acid oxidation (energy expenditure) or inhibit de novo lipogenesis.
authors.forename: Xiu
authors.initials: X
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Molecular Pharmacology for Diabetes Group, Health Innovations Research Institute and School of Health Sciences, RMIT University, PO Box 71, Melbourne, Victoria 3083, Australia. jiming.ye@rmit.edu.au.
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Ye
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; D055372:AMP-Activated Protein Kinases