Methylmercury Exposure and Diabetes - A Possible Connection
John
Science News
Mercury Compound Found In Fish Damages
Pancreatic Cells
ScienceDaily (Sep. 29, 2006) —
Researchers in Taiwan say they have established for the first time that the
mercury compound present as a contaminant in some seafood can damage
insulin-producing cells in the pancreas.
In their experiments, Shing-Hwa Liu and
colleagues exposed cell cultures of insulin-producing beta cells to
methylmercury. They used concentrations of methylmercury at about the same
levels as people would consume in fish under the U. S. Food and Drug
Administration's recommended limits.
Previous studies have shown that methylmercury is toxic to
various cells. Liu and colleagues now have added pancreatic beta cells to that
list.
"Altogether, our data clearly indicate that
methylmercury-induced oxidative stress causes pancreatic beta-cell apoptosis
(programmed cell death) and dysfunction," they said in a report scheduled for
the Aug. 21 issue of the ACS journal, Chemical Research in
Toxicology.
Liu added in an interview: "Although there was lack of a firm
clinical basis, some cellular and animal studies implied that methylmercury may
have [the] ability to injury the pancreatic beta cells. The present study
supplied the direct evidence of basic research that methylmercury-induced
oxidative stress causes pancreatic beta cell apoptosis and dysfunction. Further
research is needed on whether methylmercury exposure increases the risk of
diabetes in humans."
Toxicol Appl Pharmacol. 2009 Dec 16. [Epub ahead of
print]
Science News
ScienceDaily (Sep. 29, 2006) — Researchers in Taiwan say they have established for the first time that the mercury compound present as a contaminant in some seafood can damage insulin-producing cells in the pancreas.
Previous studies have shown that methylmercury is toxic to various cells. Liu and colleagues now have added pancreatic beta cells to that list.
"Altogether, our data clearly indicate that methylmercury-induced oxidative stress causes pancreatic beta-cell apoptosis (programmed cell death) and dysfunction," they said in a report scheduled for the Aug. 21 issue of the ACS journal, Chemical Research in Toxicology.
Liu added in an interview: "Although there was lack of a firm clinical basis, some cellular and animal studies implied that methylmercury may have [the] ability to injury the pancreatic beta cells. The present study supplied the direct evidence of basic research that methylmercury-induced oxidative stress causes pancreatic beta cell apoptosis and dysfunction. Further research is needed on whether methylmercury exposure increases the risk of diabetes in humans."
Toxicol Appl Pharmacol. 2009 Dec 16. [Epub ahead of print]Inorganic mercury causes pancreatic beta-cell death via the oxidative stress-induced apoptotic and necrotic pathways.
Chen YW, Huang CF, Yang CY, Yen CC, Tsai KS, Liu SH.
Department of Physiology and Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
Mercury is a well-known highly toxic metal. In this study, we characterize and investigate the cytotoxicity and its possible mechanisms of inorganic mercury in pancreatic beta-cells. Mercury chloride (HgCl(2)) dose-dependently decreased the function of insulin secretion and cell viability in pancreatic beta-cell-derived HIT-T15 cells and isolated mouse pancreatic islets. HgCl(2) significantly increased ROS formation in HIT-T15 cells. Antioxidant N-acetylcysteine effectively reversed HgCl(2)-induced insulin secretion dysfunction in HIT-T15 cells and isolated mouse pancreatic islets. Moreover, HgCl(2) increased sub-G1 hypodiploids and annexin-V binding in HIT-T15 cells, indicating that HgCl(2) possessed ability in apoptosis induction. HgCl(2) also displayed several features of mitochondria-dependent apoptotic signals including disruption of the mitochondrial membrane potential, increase of mitochondrial cytochrome c release and activations of poly (ADP-ribose) polymerase (PARP) and caspase 3. Exposure of HIT-T15 cells to HgCl(2) could significantly increase both apoptotic and necrotic cell populations by acridine orange/ethidium bromide dual staining. Meanwhile, HgCl(2) could also trigger the depletion of intracellular ATP levels and increase the LDH release from HIT-T15 cells. These HgCl(2)-induced cell death-related signals could be significantly reversed by N-acetylcysteine. The intracellular mercury levels were markedly elevated in HgCl(2)-treated HIT-T15 cells. Taken together, these results suggest that HgCl(2)-induced oxidative stress causes pancreatic beta-cell dysfunction and cytotoxicity involved the co-existence of apoptotic and necrotic cell death. Copyright © 2009 Elsevier Inc. All rights reserved.
PMID: 20006636 [PubMed - as supplied by publisher]
Chem Res Toxicol. 2006 Aug;19(8):1080-5.
Methylmercury induces pancreatic beta-cell apoptosis and dysfunction.
Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH.
Institute of Toxicology, Department of Laboratory Medicine, and Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan.
Mercury is a well-known toxic metal, which induces oxidative stress. Pancreatic beta-cells are vulnerable to oxidative stress. The pathophysiological effect of mercury on the function of pancreatic beta-cells remains unclear. The present study was designed to investigate the effects of methylmercury (MeHg)-induced oxidative stress on the cell viability and function of pancreatic beta-cells. The number of viable cells was reduced 24 h after MeHg treatment in a dose-dependent manner with a range from 1 to 20 microM. 2',7'-Dichlorofluorescein fluorescence as an indicator of reactive oxygen species (ROS) formation after exposure of HIT-T15 cells or isolated mouse pancreatic islets to MeHg significantly increased ROS levels. MeHg could also suppress insulin secretion in HIT-T15 cells and isolated mouse pancreatic islets. After 24 h of exposure to MeHg, HIT-T15 cells had a significant increase in mercury levels with a dose-dependent manner. Moreover, MeHg displayed several features of cell apoptosis including an increase of the sub-G1 population and annexin-V binding. Treatment of HIT-T15 cells with MeHg resulted in disruption of the mitochondrial membrane potential and release of cytochrome c from the mitochondria to the cytosol and activation of caspase-3. Antioxidant N-acetylcysteine effectively reversed the MeHg-induced cellular responses. Altogether, our data clearly indicate that MeHg-induced oxidative stress causes pancreatic beta-cell apoptosis and dysfunction.
PMID: 16918248 [PubMed - indexed for MEDLINE]
Diabetes. 2006 Jun;55(6):1614-24.
The role of phosphoinositide 3-kinase/Akt signaling in low-dose mercury-induced mouse pancreatic beta-cell dysfunction in vitro and in vivo.
Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH.
Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, 10043, Taiwan.
The relationship between oxidation stress and phosphoinositide 3-kinase (PI3K) signaling in pancreatic beta-cell dysfunction remains unclear. Mercury is a well-known toxic metal that induces oxidative stress. Submicromolar-concentration HgCl(2) or methylmercury triggered reactive oxygen species (ROS) production and decreased insulin secretion in beta-cell-derived HIT-T15 cells and isolated mouse islets. Mercury increased PI3K activity and its downstream effector Akt phosphorylation. Antioxidant N-acetyl-l-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. These results indicate that both PI3K and ROS independently regulated Akt signaling-related, mercury-induced insulin secretion inhibition. We next observed that 2- or 4-week oral exposure to low-dose mercury to mice significantly caused the decrease in plasma insulin and displayed the elevation of blood glucose and plasma lipid peroxidation and glucose intolerance. Akt phosphorylation was shown in islets isolated from mercury-exposed mice. NAC effectively antagonized mercury-induced responses. Mercury-induced in vivo effects and increased blood mercury were reversed after mercury exposure was terminated. These results demonstrate that low-dose mercury-induced oxidative stress and PI3K activation cause Akt signaling-related pancreatic beta-cell dysfunction.
PMID: 16731823 [PubMed - indexed for MEDLINE]