Joseph F. Ndisang
University of Saskatchewan College of Medicine, Canada
Title: Heme oxygenase ameliorates cardio-renal complications in diabetic animals
Biography
Biography: Joseph F. Ndisang
Abstract
Impaired glucose metabolism and dysfunctional insulin signaling are forerunners of cardio-renal complications. Upregulating heme-oxygenase (HO) with HO-inducers potentiates insulin signaling and improved glucose metabolism in type-1 and type-2 diabetic models. Particularly, pro-inflammatory/oxidative mediators including: (i) cytokines (TNF-α, IL-6, IL-1β), (ii) chemokines (MCP-1, MIP-1α), (iii) macrophage-M1 infiltration, (iv) NF-κB, AP-1, AP-2, cJNk and 8-isoprostane were suppressed by the HO-inducer, hemin whereas components of insulinsignaling such as IRS-1, GLUT4, PI3K and PKB were robustly enhanced. Furthermore, hemin reduced insulin/glucose intolerance. These were associated with the amelioration of cardiac lesions (hypertrophy, collagen deposition in cardiomyocytes and left ventricular longitudinal muscle-fiber thickness) and the improvement of renal lesions (glomerulosclerosis, tubular necrosis, tubular vacuolization, interstitial macrophage infiltration). In addition, the HO-inducer, hemin and abrogated pro-fibrotic/extracellular-matrix proteins like collagen and fibronectin that deplete nephrin, a protein which forms the scaffolding of the podocyte slit-diaphragm for filtration. Correspondingly, improved cardiac hemodynamics and reduced albuminuria/proteinuria and enhanced creatinine clearance was observed suggesting improved cardiac and renal functions. Collectively, these data suggest that HO-inducers may be explored in the search for novel and effective remedies against cardio-renal complications.