RESUMO
Abstract Fluoride (F) has been widely used to control dental caries, and studies suggest beneficial effects against diabetes when a low dose of F is added to the drinking water (10 mgF/L). Objectives This study evaluated metabolic changes in pancreatic islets of NOD mice exposed to low doses of F and the main pathways altered by the treatment. Methodology In total, 42 female NOD mice were randomly divided into two groups, considering the concentration of F administered in the drinking water for 14 weeks: 0 or 10 mgF/L. After the experimental period, the pancreas was collected for morphological and immunohistochemical analysis, and the islets for proteomic analysis. Results In the morphological and immunohistochemical analysis, no significant differences were found in the percentage of cells labelled for insulin, glucagon, and acetylated histone H3, although the treated group had higher percentages than the control group. Moreover, no significant differences were found for the mean percentages of pancreatic areas occupied by islets and for the pancreatic inflammatory infiltrate between the control and treated groups. Proteomic analysis showed large increases in histones H3 and, to a lesser extent, in histone acetyltransferases, concomitant with a decrease in enzymes involved in the formation of acetyl-CoA, besides many changes in proteins involved in several metabolic pathways, especially energy metabolism. The conjunction analysis of these data showed an attempt by the organism to maintain protein synthesis in the islets, even with the dramatic changes in energy metabolism. Conclusion Our data suggests epigenetic alterations in the islets of NOD mice exposed to F levels comparable to those found in public supply water consumed by humans.
RESUMO
Terapias a base de glicocorticóides estão freqüentemente associadas a alteração da sensibilidade à insulina. No presente trabalho avaliamos alguns parâmetros metabólicos como glicose, insulina, proteínas e colesterolplasmáticos em ratos tratados com dexametasona (DEX) (1mg/kg, peso corpóreo, ip.) por diferentes períodos de tempo (24h, 72h e 120h). Os ratos tratados com dexametasona apresentaram resistência periférica à insulina após 24h de administração da droga como indicam os valores de insulina plasmática de jejum (1,3 vs. 6,8 ng/ml para ratos controle [CTL] e DEX, respectivamente) e do índice HOMA. Resistência periférica à insulina adicional ocorre até o final do tratamento nos ratos DEX. A glicemia permanece moderadamente elevada até o período de 72h. Entretanto, observa-se marcante hiperglicemia após 120h (79 vs. 160 mg/dl para ratos CTL e DEX, respectivamente). Aumento significativo dos níveis de proteínas totais e albuminas plasmáticas ocorre a partir de 72h de tratamento e de colesterol total a partir de 120h. Glicogênio e gordura hepáticos aumentam de maneira tempo-dependente nos ratos DEX. Correlação negativa foi observada entre os valores de insulinemia de jejum e peso nos grupos tratados com dexametasona (r > 0,95). Portanto, administração de dexametasona, 1mg/kg, induz resistência periférica à insulina de maneira tempo-dependente a partir de 24h e aumento dos níveis circulantes de glicose e proteínas plasmáticos após 72h de tratamento.
Glucocorticoid therapies are often associated with insulin sensitivity alteration. In the present study we evaluated some metabolical parameters such as plasma glucose, insulin, protein and cholesterol levels in ratstreated with dexamethasone (DEX) (1mg/kg, body weight, ip.) in different periods (24h, 72h and 120h). Dexamethasonetreated rats show peripherical resistance after 24h of drug administration as indicated by the fasting plasma insulin values (1.3 vs.6.8 ng/ml for controls [CTL] and DEX rats, respectively) and by HOMA index. Additional peripheral insulin resistance occurred until the end of treatment in DEX rats. The glycaemia remained slightly elevated until 72h period. However, marked hyperglycaemia was observed after 120h (79 vs.160 mg/dl for CTL and DEX rats, respectively). Significantly increase of plasma albumin and total proteins levels occurred from 72h of treatment and total cholesterol from 120h. Hepatic glycogen and hepatic fat increased in a time-dependent manner in DEX rats. Negative correlation was observed between fasting insulin and body weight values in dexamethasone-treated groups (r > 0.95). Therefore, dexamethasone administration, 1mg/kg, induces insulin peripheral resistance in a time-dependent manner from 24h and increase of circulating plasma glucose and proteins levels after 72h of treatment.