کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2793635 1155163 2007 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Small Molecule Harmine Is an Antidiabetic Cell-Type-Specific Regulator of PPARγ Expression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
The Small Molecule Harmine Is an Antidiabetic Cell-Type-Specific Regulator of PPARγ Expression
چکیده انگلیسی

SummaryPPARγ is the master regulator of adipogenesis and the molecular target of the thiazolidinedione antidiabetic drugs. By screening for compounds that promote adipogenesis, we identified a small molecule that targets the PPARγ pathway by a distinct mechanism. This molecule, harmine, is not a ligand for the receptor; rather, it acts as a cell-type-specific regulator of PPARγ expression. Administration of harmine to diabetic mice mimics the effects of PPARγ ligands on adipocyte gene expression and insulin sensitivity. Unlike thiazolidinediones, however, harmine does not cause significant weight gain or hepatic lipid accumulation. Molecular studies indicate that harmine controls PPARγ expression through inhibition of the Wnt signaling pathway. This work validates phenotypic screening of adipocytes as a promising strategy for the identification of bioactive small molecules and suggests that regulators of PPARγ expression may represent a complementary approach to PPARγ ligands in the treatment of insulin resistance.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 5, Issue 5, 9 May 2007, Pages 357–370
نویسندگان
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