Abstract
A recent study suggested that simultaneous exposure of non-diabetics to high levels of dioxins and mercury increases their risk of insulin resistance. An increased incidence of diabetes existed in patients with documented Minamata disease (methylmercury poisoning) in Japan. Previous in vitro studies have shown that HgCl2 altered intracellular Ca2+ homeostasis in pancreatic β-cells isolated from mouse islets, and decreased insulin secretion from secretion granules isolated from toadfish islets. Mercury is a well-known toxic metal, which induces oxidative stress. The toxicity of mercury in islets is highly related to oxidative stress. It has been shown that 8-hydroxy-2’-deoxyguanosine, a biomarker of oxidative DNA damage, is significantly elevated in urine samples of people from mercury-contaminated areas. Our studies have also shown that submicromolar-concentration HgCl2 or methylmercury is capable of affecting the islet β-cell function and survival through an oxidative stress pathway in vivo and in vitro. Low-dose mercury induced mouse pancreatic islet β-cell dysfunction through a phosphoinositide 3-kinase (PI3K)-activated or oxidative stress-triggered Akt pathway in cell culture and animal models. Antioxidant N-acetyl-L-cysteine prevented mercury-induced insulin secretion inhibition and Akt phosphorylation. Moreover, methylmercury could induce oxidative stress-triggered β-cell apoptosis and death. HgCl2 could also be capable of inducing the oxidative stress-related insulin secretion suppression and cell death in pancreatic β-cells. The further evidences indicate that HgCl2 enters β-cells and triggers oxidative stress to induce cell death through both apoptotic and necrotic pathways. Taken together, these observations provide evidences to confirm the possibility that mercury is an environmental risk factor for diabetes.
