Cannabinoid Receptor 1 Blockade Ameliorates Albuminuria in Experimental Diabetic Nephropathy

• DOI: 10.2337/db09-1336
• Publication Date: 2010-01-13T04:34:04Z
• Authors: Federica Barutta; Alessandro Corbelli; Raffaella Mastrocola; Roberto Gambino; Vincenzo Di Marzo; Silvia Pinach; Maria Pia Rastaldi; Paolo Cavallo Perin; Gabriella Gruden
• Keywords: Nephrin; AM251; Podocin; Albuminuria

OBJECTIVE Cannabinoid receptor 1 (CB1) is localized in the central nervous system and peripheral tissues involved energy metabolism control. However, CB1 receptors are also expressed at low level within glomeruli, aim of this study was to investigate their potential relevance pathogenesis proteinuria experimental type diabetes. RESEARCH DESIGN AND METHODS Streptozotocin-induced diabetic mice were treated with N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,3-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), a selective CB1-receptor antagonist, dosage mg · kg−1 day−1 via intraperitoneal injection for 14 weeks. Urinary albumin excretion measured by enzyme-linked immunosorbent assay. expression studied immunohistochemistry, immunoblotting, real-time PCR. Expression nephrin, podocin, synaptopodin, zonula occludens-1 (ZO-1) assessed immunofluorescence Fibronectin, transforming growth factor-β1 (TGF-β1), connective tissue factor (CTGF) mRNA levels quantitated RESULTS In mice, overexpressed predominantly glomerular podocytes. Blockade did not affect body weight, blood glucose, pressure either or control mice. Albuminuria increased compared animals significantly ameliorated treatment AM251. Furthermore, blockade completely prevented diabetes-induced downregulation ZO-1. By contrast overexpression fibronectin, TGF-β1, CTGF renal cortex unaltered AM251 administration. CONCLUSIONS diabetes, podocytes, ameliorates albuminuria possibly prevention ZO-1 loss.