Joseph Fomusi Ndisang
University of Saskatchewan, Canada
Title: Role of heme oxygenase in insulin signaling and glucose metabolism
Biography
Biography: Joseph Fomusi Ndisang
Abstract
Impaired insulin signaling and deregulated glucose metabolism are amongst the hallmarks in diabetes. Here, we report the effects of the cytoprotective enzyme, heme-oxygenase, (HO) on insulin signaling and glucose metabolism. The administration of the HO-inducer, hemin, to streptozotocin-induced diabetic animals normalized hyperglycemia and the potentiated important proteins implicated in the insulin-signal transduction pathway such as IRS-1, PI3K and GLUT4. Interestingly, the anti-diabetic effects of hemin was accompanied by enhanced levels of adiponectin, improved insulin sensitivity and reduced glucose intolerance. These were associated with the reduction of oxidative/inflammatory mediators like 8-isoprostance, nuclear-factor-kappaB, activating-protein (AP-1), AP-2 and c-Jun-NH2-terminal-kinase. Furthermore, hemin suppressed the pro-inflammatory macrophage-M1-phenotype alongside several pro-inflammatory agents, chemokines and cytokines including macrophage-inflammatory-protein-1-alpha (MIP-1α), macrophage-chemoattractant-protein-1 (MCP-1), TNF-α, IL-1β and IL-6. Conversely, hemin significantly enhanced the anti-inflammatory macrophage-M2-phenotype and IL-10. We conclude that upregulating the HO system abates hyperglycemia in diabetic animals by nullifying inflammation and oxidative stress, while concomitantly potentiating insulin signalling and glucose metabolism. Thus HO-inducers may be explored in the search for novel remedied against type-1 diabetes.
