title: Inhibition of HDAC3 as a strategy for developing novel diabetes therapeutics.
abstract: Modulation of histone deacetylase (HDAC) activity has been implicated as a potential therapeutic strategy for multiple diseases. Recent studies have put a greater spotlight on metabolic diseases, in particular Type 1 and Type 2 diabetes, as potential indications for which HDAC inhibition could be beneficial. Evidence suggests that inhibition of HDAC3 protects β-cells from cytokine-induced apoptosis, an important event in the development of Type 1 diabetes. On the other hand, the pathogenesis of Type 2 diabetes involves a combination of peripheral insulin resistance and pancreatic β-cell failure. Again, data from the literature indicate that HDAC3 regulates genes involved in key metabolic events. Together, these results suggest that selective inhibition of HDAC3 may be an attractive strategy for targeting these diseases.
authors.affiliation: Chemical Biology Program, Harvard Medical School, Boston, MA, USA.
authors.forename: Bennett C
authors.initials: BC
authors.lastname: Meier
authors.forename: Bridget K
authors.initials: BK
authors.lastname: Wagner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000235:genetics; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000473:pathology; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D000099186:Histone Deacetylase 3
chemical_list: D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D034741:RNA, Small Interfering; D000099186:Histone Deacetylase 3; C012589:trichostatin A