Peroxisome proliferator-activated receptor γ (PPARγ) is a central regulator of adipocyte differentiation and is the principle target of the thiazolidinedione (TZD) class of antidiabetic drugs.1 Harmine is a β-carboline alkaloid that was first isolated from seeds of Peganum harmala (Syrian rue) and Banisteriopsis caapi. Recent work indicates that harmine is a unique regulator of PPARγ expression that acts by inhibiting the Wnt signalling pathway in a cell-specific manner.2 Administration of harmine (30 mg/kg) to obese db/db mice resulted in reduced blood glucose, free fatty acids, and triglyceride levels, delayed hyperglycemia, and improved insulin sensitivity. Harmine also attenuates inflammatory gene expression (TNF-α, IL-1β, iNOS) and macrophage accumulation in adipose tissue.2
1.Hauner, H.The mode of action of thiazolidinedionesDiabetes Metab. Res. Rev.18(Suppl. 2)S10-S15(2002)
2.Waki, H., Park, K.W., Mitro, N., et al.The small molecule harmine is an antidiabetic cell-type-specific regulator of PPARγ expressionCell Metab.5(5)357-370(2007)
