Departments of Physiology, University of Saskatchewan College of Medicine,Canada
Title: Heme oxygenase is a novel strategy against cardio-renal complications in diabetic animals
Biography: Joseph Fomusi Ndisang
In diabetic subjects, dysfunctional insulin signaling and impaired glucose metabolism are associated with alterations and function of the heart and kidneys. We recently reported that upregulating heme-oxygenase (HO) potentiates insulin signaling and improve glucose metabolism in different animal models of type-1 and type-2 diabetes. Particularly, HO-inducers suppressed inflammatory/oxidative mediators such as cytokines (TNF-α, IL-6, IL-1β), chemokines (MCP-1, MIP-1α), macrophage-M1 infiltration, NF-κB, AP-1, AP-2, cJNk and 8-isoprostane but potentiated insulin-signaling proteins (IRS-1, GLUT4, PI3K, PKB) and reduced insulin/glucose intolerance. These were associated with reduced cardiac lesions (hypertrophy, collagen deposition in cardiomyocytes and left ventricular longitudinal muscle-fiber thickness) and renal lesions (glomerulosclerosis, tubular necrosis, tubular vacuolization, interstitial macrophage infiltration and 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 proteinuria was observed suggesting improved cardiac and renal functions.
These data suggest that HO may be explored in the search for novel and effective remedies against cardio-renal complications