Role of heme oxygenase in inflammation, insulin-signalling, diabetes and obesity.
Diabetes and obesity are chronic conditions associated with elevated oxidative/inflammatory activities with a continuum of tissue insults leading to more severe cardiometabolic and renal complications including myocardial infarction and end-stage-renal damage. A common denominator of these chronic conditions is the enhanced the levels of cytokines like tumour necrosis factor-alpha (TNF-alpha), interleukin (IL-6), IL-1beta and resistin, which in turn activates the c-Jun-N-terminal kinase (JNK) and NF-kappaB pathways, creating a vicious cycle that exacerbates insulin resistance, type-2 diabetes and related complications. Emerging evidence indicates that heme oxygenase (HO) inducers are endowed with potent anti-diabetic and insulin sensitizing effects besides their ability to suppress immune/inflammatory response. Importantly, the HO system abates inflammation through several mechanisms including the suppression of macrophage-infiltration and abrogation of oxidative/inflammatory transcription factors like NF-kappaB, JNK and activating protein-1. This review highlights the mechanisms by which the HO system potentiates insulin signalling, with particular emphasis on HO-mediated suppression of oxidative and inflammatory insults. The HO system could be explored in the search for novel remedies against cardiometabolic diseases and their complications.
Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada. joseph.ndisang@usask.ca
Joseph Fomusi
JF
Ndisang
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress; D015398:Signal Transduction
D007328:Insulin; D007527:Isoenzymes; D016328:NF-kappa B; D006419:Heme Oxygenase (Decyclizing)