title: Emerging roles of cadmium and heme oxygenase in type-2 diabetes and cancer susceptibility.
abstract: Many decades after an outbreak of severe cadmium poisoning, known as Itai-itai disease, cadmium continues to pose a significant threat to human health worldwide. This review provides an update on the effects of this environmental toxicant cadmium, observed in numerous populations despite modest exposure levels. In addition, it describes the current knowledge on the link between heme catabolism and glycolysis. It examines novel functions of heme oxygenase-2 (HO-2) that protect against type 2-diabetes and obesity, which have emerged from diabetic/obese phenotypes of the HO-2 knockout mouse model. Increased cancer susceptibility in type-2 diabetes has been noted in several large cohorts. This is a cause for concern, given the high prevalence of type-2 diabetes worldwide. A lifetime exposure to cadmium is associated with pre-diabetes, diabetes, and overall cancer mortality with sex-related differences in specific types of cancer. Liver and kidney are target organs for the toxic effects of cadmium. These two organs are central to the maintenance of blood glucose levels. Further, inhibition of gluconeogenesis is a known effect of heme, while cadmium has the propensity to alter heme catabolism. This raises the possibility that cadmium may mimic certain HO-2 deficiency conditions, resulting in diabetic symptoms. Intriguingly, evidence has emerged from a recent study to suggest the potential interaction and co-regulation of HO-2 with the key regulator of glycolysis: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4). HO-2 could thus be critical to a metabolic switch to cancer-prone cells because the enzyme PFKFB and glycolysis are metabolic requirements for cell proliferation and resistance to apoptosis.
authors.affiliation: Center for Kidney Disease Research, University of Queensland School of Medicine, Brisbane, Australia. sj.satarug@yahoo.com.au
authors.forename: Soisungwan
authors.initials: S
authors.lastname: Satarug
authors.forename: Michael R
authors.initials: MR
authors.lastname: Moore
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002104:Cadmium / Q000009:adverse effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D004198:Disease Susceptibility / Q000097:blood / Q000201:enzymology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000201:enzymology*
chemical_list: D001786:Blood Glucose; D002104:Cadmium; D006419:Heme Oxygenase (Decyclizing)