A Mechanistic Approach Elaborating the Association of Heavy Metals-Induced Oxidative Stress with Insulin Resistance Susceptibility A Mechanistic Approach Elaborating the Association of Heavy Metals-Induced Oxidative Stress with Insulin Resistance Susceptibility

Abstract

Heavy metals are widely distributed in the environment and cause various life threatening diseases like metabolic syndrome (MS) or Diabetes Mellitus (DM). Various industrial, mining and pharmaceutical operations drain large quantities of toxic heavy metals in soil, air and water and rendering it contaminated and offer a store house for diseases. Investigations show that high blood serum levels of heavy metals cause insulin resistance in large number of population worldwide. Cd is known to cause mitochondrial malfunctioning, and increased level of proinflammatory mediators like IL-1β, IL-6, and TNF-α. Likewise, As is known to transduce various signaling factors such as NFκB, MPAK, TNFα, P13K, PKB/Akt and GLUT4 that ultimately disrupt the glucose levels and activity of insulin in the body leading to insulin resistance. While Ni exposure cause free radicals production which impair normal functioning of DNA repair enzymes casing hyperglycemia and insulin resistance in rats model indicating that Ni plays a major role as precipitating factor in insulin resistance. Studies revealed a large number of iNOS and cGMP levels in pancreatic islets that appear to cause dysregulation of glucose through ROS pathway leading to insulin resistance. Mercury (Hg) on the other hand is known to causes insulin resistance through the mechanism of oxidative stress which results in large expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage. Glutathione (GSH), total protein thiols, and enzymes like glutathione peroxidase and superoxide dismutase levels are also markedly high. In the last, Lead (Pb) causes insulin resistance through the ROS which causes oxidative stress and ultimately causes insulin resistance in suspected individuals.