Dissecting copper homeostasis in diabetes mellitus

Abstract

Diabetes Mellitus (DM) is characterized by elevated blood glucose levels (hyperglycemia). It can occur due to impaired secretion or action of the hormone insulin, which is produced by pancreatic beta-cells to promote the entry of glucose into the cells. It is known that hyperglycemia has an important role in the production of reactive oxygen species in all types of DM and that an imbalance of transition metal as Cu and Fe plays a pivotal role in stimulating the oxidative stress. Different levels of some transition metals, as Cu, Fe, Mn, and Zn has been reported comparing diabetic animal models with the control group. An increased Cu status is also described in diabetic patients. Homeostasis of Cu depends on distinct proteins, where Cu(I)-ATPases are important transmembrane proteins for acquisition, active transport, distribution and elimination of Cu ions. In this review we first provide an overview of the literature about the relationship between diabetes and copper, the modulation of Cu(I)-ATPases activity and protein expression in DM, to next discuss the alternative treatments for diabetes using Cu chelation. V C 2017 IUBMB Life, 69(4): [255][256][257][258][259][260][261][262] 2017

Current Biomedical Use of Copper Chelation Therapy

“…Transition between Cu(I) and Cu(II) leads to the production of reactive oxygen species (ROS) and to consequent peroxidation of lipids, DNA damage leading to cell death. Therefore, copper homeostasis maintenance using copper chelators may represent a strategy for diabetes treatment [16]. A series of pre-clinical and clinical studies demonstrated the potential of trientine in reducing some of the clinical and pathological consequences of diabetes, such as heart failure [88].…”

“…ATPase copper-transporting alpha (ATP7A) and ATPase copper-transporting beta (ATP7B) are key players in copper homeostasis being required for copper delivery to the secretory pathway and for efflux of excess copper from the cell. Deregulation of this delicate balance that maintains copper homeostasis has been associated with The aim of the present review is to provide a global overview on the main different chelation therapy approaches which have been evaluated for the treatment of the diseases in which copper imbalance has a key role in the onset of the pathology, including genetic diseases of copper metabolism such as Wilson's diseases [8], neurodegenerative diseases such as Alzheimer's and Parkinson's diseases [14], idiopathic pulmonary fibrosis [15], diabetes [16], and different forms of cancer [17].…”

Is copper a new target to counteract the progression of chronic diseases?

“…Recent results indicate that altered serum Cu homeostasis has an important role in diabetes, obesity, metabolic syndrome and non-alcoholic fatty-liver disease (NAFLD). 25,26 In fact, diabetes mellitus and obesity are known to correlate with an imbalance of transition metals, including Cu. 27 Oxidative stress, insulin resistance, end-product molecules, adipokines, pro-inflammatory cytokines and mitochondrial dysfunction are all related to higher Cu serum levels and are implicated in the development and progression of several chronic inflammatory diseases.…”

The Influence of Taurine Supplementation on Serum and Tissular Fe, Zn and Cu Levels in Normal and Diet-Induced Insulin-Resistant Rats

“…•− , whereas interaction with H 2 O 2 may generate OH˙in the Fenton and Haber-Weiss reactions [11]. The transition of Cu(I) and Cu(II) may result in the generation of ROS and it may further lead to the oxidation of protein and other molecules [12,13].…”