Effect of Fluoride on the Secretion of Insulin in the Rat

Menoyo, Inés; Rigalli, Alfredo; Puche, R. C.

doi:10.1055/s-0031-1296888

Cited by 10 publications

(9 citation statements)

References 12 publications

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“…Indeed, F − -mediated decrease in protein synthesis and/or secretion has been well-documented [27], [28], [32], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73]. Importantly, we demonstrated a decrease in enamel matrix transcripts during the maturation stage.…”

Section: Discussionsupporting

confidence: 63%

The Acid Test of Fluoride: How pH Modulates Toxicity

Sharma¹,

Tsuchiya

Skobe³

et al. 2010

PLoS ONE

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BackgroundIt is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F−). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F−. Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F− into cells. Here, we asked if F− was more toxic at low pH, as measured by increased cell stress and decreased cell function.Methodology/Principal FindingsTreatment of ameloblast-derived LS8 cells with F− at low pH reduced the threshold dose of F− required to phosphorylate stress-related proteins, PERK, eIF2α, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F− dose and pH. Luciferase secretion significantly decreased within 2 hr of F− treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F− in their drinking water exhibited increased stress-mediated phosphorylation of eIF2α in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH∼7.2). Intriguingly, F−-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn). In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected.ConclusionsThe low pH environment of maturation stage ameloblasts facilitates the uptake of F−, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis.

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Section: Discussionsupporting

confidence: 63%

The Acid Test of Fluoride: How pH Modulates Toxicity

Sharma¹,

Tsuchiya

Skobe³

et al. 2010

PLoS ONE

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“…The effect was verified with isolated Langerhans islets and with slices of pancreas, indicating that F probably interferes with calmodulin, cAMP, and protein kinase C signaling pathways [5]. The administration of F in the drinking water did not produce an increase in basal levels of glucose, but tolerance to glucose after a glucose tolerance test was hindered by the presence of fluoride [7].…”

Section: Discussionmentioning

confidence: 84%

“…Fluoride has been reported to produce hyperglycemia as a consequence of an inhibitory effect of fluoride on the secretion of insulin by an alteration in the intracellular signaling pathway related to the secretion of insulin [5]. This effect was observed when plasma fluoride concentration is higher than 5 μM after a single dose of NaF in rats (7.6 mg F/kg body weight) and in humans (60 mg NaF) [6] and also after the administration of drinking water with fluoride 100 ppm to rats for 30 days [7].…”

Section: Introductionmentioning

confidence: 99%

Effect of Fluoridated Water on Plasma Insulin Levels and Glucose Homeostasis in Rats with Renal Deficiency

Lupo

Buzalaf

Rigalli

2010

Biol Trace Elem Res

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Glucose intolerance in fluorosis areas and when fluoride is administered for the treatment of osteoporosis has been reported. Controlled fluoridation of drinking water is regarded as a safe and effective measure to control dental caries. However, the effect on glucose homeostasis was not studied so far. The aim of this study was to evaluate the effect of the intake of fluoridated water supply on glucose metabolism in rats with normal and deficient renal function. Male Sprague-Dawley rats were divided into eight groups of four rats. Renal insufficiency was induced in four groups (NX) which received drinking water containing 0, 1, 5, and 15 ppm F (NaF) for 60 days. Four groups with simulated surgery acted as controls. There were no differences in plasma glucose concentration after a glucose tolerance test between controls and NX rats and among rats with different intakes of fluoride. However, plasma insulin level increased as a function of fluoride concentration in drinking water, both in controls and in NX rats. It is concluded that the consumption of fluoridated water from water supply did not affect plasma glucose levels even in cases of animals with renal disease. However, a resistance to insulin action was demonstrated.

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“…Summarizing, fluoride affects glucose and insulin levels in a dose and time dependent fashion—an increase or decrease can be observed. Thus, reported hyperglycemia may derive from an inhibitory effect of fluoride on the secretion of insulin, via altered intracellular signaling pathways related to insulin secretion (Menoyo et al 2005). This effect was observed when plasma fluoride concentration was higher than 5 μM after a single dose of NaF in rats (7.6 mg F/kg body weight) and in humans (60 mg NaF) (Rigalli et al 1990) and also in rats after administration of NaF (100 ppm) in drinking water for 30 days (Rigalli et al 1992).…”

Section: Discussionmentioning

confidence: 99%

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues

et al. 2017

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The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

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Effect of Fluoride on the Secretion of Insulin in the Rat

Cited by 10 publications

References 12 publications

The Acid Test of Fluoride: How pH Modulates Toxicity

The Acid Test of Fluoride: How pH Modulates Toxicity

Effect of Fluoridated Water on Plasma Insulin Levels and Glucose Homeostasis in Rats with Renal Deficiency

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues

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