Global Experts Meeting On Diabetes, Hypertension & Metabolic Syndrome

Heme oxygenase (HO) is a cytoprotective protein. Our recent studies indicate that upregulating heme-oxygenase (HO) potentiates several components of insulin signaling such as IRS-1, PI3K and PKB and improve glucose metabolism by reducing (i) insulin/glucose intolerance (ii) increasing insulin sensitivity and the inability of insulin to enhance GLUT4 in animal models of type-1 and type-2 diabetes including (i) streptozotocin-induced diabetic rats, (ii) Zucker diabetic fatty rats (ZDF). These were associated with: (i) the suppression inflammatory cytokines like TNF-α, IL-6, IL-1β and chemokines such as MCP-1 and MIP-1α, (ii) the attenuation of pro-oxidative/inflammatory transcriptions factors and mediators including NF-κB, activating-protein (AP)-1, AP-2, and c-Jun-N-terminal-kinase and 8-isoprostane. Correspondingly, HO reduced renal histological lesions such as glomerulosclerosis, tubular necrosis, tubular vacuolization, interstitial macrophage infiltration as well as pro-fibrotic/extracellular-matrix proteins like collagen and fibronectin that deplete nephrin, an important transmembrane protein which forms the scaffolding of the podocyte slit-diaphragm allowing ions to filter but not massive excretion of proteins. These were accompanied by the reduction of proteinuria/albuminuria, but the potentiation of creatinine clearance, suggesting improved renal function.

Collectively these data suggest an important role of HO in the preservation of kidney function in diabetes.