Fluoride Exposure Impairs Glucose Tolerance Via Decreased Insulin Expression And Oxidative Stress. Export

@article{citeulike:5037328, abstract = {Chronic exposure to high fluoride (F(-)) may lead to local tissue disturbances, known as fluorosis. F(-) is an oxidising agent and a well-known reversible enzymatic inhibitor that interferes with the enzyme activity of at least 80 proteins. The goals of the current study were to evaluate whether F(-) exposure affected the oral glucose tolerance test (OGTT) in C57BL6 mice; and to determine the mechanisms at work in glucose homeostasis at the cellular level, in mouse pancreatic beta-cells (betaTC-6) exposed to F(-). Mice were exposed to 45mg l-1 F- via drinking water, and cells were exposed for 12h to NaF (equivalent to 0, 0.007, 0.045, 0.180, 1.35 or 2.26mM F(-)) at a basal or stimulatory glucose concentration (2.8 or 16.6mM, respectively). Mice showed an impaired glucose tolerance after 4 weeks of F(-) exposure, while beta-cells exposed to 1.35 and 2.26mM F(-) had significantly lower insulin mRNA expression and subsequent secretion in the presence of the stimulatory glucose concentration. The glucose transporter in beta-cells was not affected by F- exposure. However, oxidative stress evaluated by the functional activity of superoxide dismutase (SOD) and generation of the superoxide anion (O(2)(-)), showed significantly decreased SOD activity, in a dose-dependent manner. This was accompanied by an increase in the generation of O(2)(-), and decreased mitochondrial membrane potential in F(-) exposed cells. Insulin secretion was lower in beta-cells exposed to F(-), even in the presence of glibenclamide, the ATP-sensitive K(+) (K(ATP)) channel blocker, suggesting downregulation of the K(ATP) channel in the cell. Exposure to high levels of F(-) in drinking water may decrease insulin mRNA and its secretion from beta-cells, and might therefore affect the OGGT.}, author = {Garc\'{\i}a-Montalvo, Eliud A. and Reyes-P\'{e}rez, Hugo and Del Razo, Luz M.}, citeulike-article-id = {5037328}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.tox.2009.06.008}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19540901}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19540901}, day = {18}, doi = {10.1016/j.tox.2009.06.008}, issn = {0300-483X}, journal = {Toxicology}, keywords = {fluoride, glucose, insulin}, month = {June}, posted-at = {2009-07-01 23:19:08}, priority = {2}, title = {Fluoride Exposure Impairs Glucose Tolerance Via Decreased Insulin Expression And Oxidative Stress.}, url = {http://dx.doi.org/10.1016/j.tox.2009.06.008}, year = {2009} }

TY - JOUR ID - citeulike:5037328 L3 - citeulike-article-id:5037328 N2 - Chronic exposure to high fluoride (F(-)) may lead to local tissue disturbances, known as fluorosis. F(-) is an oxidising agent and a well-known reversible enzymatic inhibitor that interferes with the enzyme activity of at least 80 proteins. The goals of the current study were to evaluate whether F(-) exposure affected the oral glucose tolerance test (OGTT) in C57BL6 mice; and to determine the mechanisms at work in glucose homeostasis at the cellular level, in mouse pancreatic beta-cells (betaTC-6) exposed to F(-). Mice were exposed to 45mg l-1 F- via drinking water, and cells were exposed for 12h to NaF (equivalent to 0, 0.007, 0.045, 0.180, 1.35 or 2.26mM F(-)) at a basal or stimulatory glucose concentration (2.8 or 16.6mM, respectively). Mice showed an impaired glucose tolerance after 4 weeks of F(-) exposure, while beta-cells exposed to 1.35 and 2.26mM F(-) had significantly lower insulin mRNA expression and subsequent secretion in the presence of the stimulatory glucose concentration. The glucose transporter in beta-cells was not affected by F- exposure. However, oxidative stress evaluated by the functional activity of superoxide dismutase (SOD) and generation of the superoxide anion (O(2)(-)), showed significantly decreased SOD activity, in a dose-dependent manner. This was accompanied by an increase in the generation of O(2)(-), and decreased mitochondrial membrane potential in F(-) exposed cells. Insulin secretion was lower in beta-cells exposed to F(-), even in the presence of glibenclamide, the ATP-sensitive K(+) (K(ATP)) channel blocker, suggesting downregulation of the K(ATP) channel in the cell. Exposure to high levels of F(-) in drinking water may decrease insulin mRNA and its secretion from beta-cells, and might therefore affect the OGGT. JF - Toxicology SN - 0300-483X TI - Fluoride Exposure Impairs Glucose Tolerance Via Decreased Insulin Expression And Oxidative Stress. KW - fluoride KW - glucose KW - insulin AU - García-Montalvo, Eliud AU - Reyes-Pérez, Hugo AU - Del Razo, Luz PY - 2009/06/18/ UR - http://dx.doi.org/10.1016/j.tox.2009.06.008 ER -