Arsenite in Drinking Water Alters Glucose Tolerance, Insulin Secretion, HOMA-IR and Oxidative Stress in Offspring

Presentation Number: SUN 583
Date of Presentation: April 2nd, 2017

Maria Marta Bonaventura*1, Nadia Bourguignon1, Marianne Bizzozzero Hiriart2, Clara Ventura3, Clara Cocca3, Carlos Libertun2 and Victoria A Lux-Lantos1
1Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina, 2Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina, 3Universidad de Buenos Aires, CABA

Abstract

The major source of human exposure to inorganic Arsenic is drinking water. We determined the effects of exposure to Arsenic from conception to adulthood on the glucose metabolism and oxidative stress in rats. We administered sodium arsenite in drinking water [0 (C), 5 (A5) or 50 ppm (A50)] to Sprague Dawley rats from gestational day 1 to weaning of their offspring. Offspring continued with the same treatment as their mothers. Glucose tolerance and Insulin secretion test (TTG and IST, 2 g glucose/kg body weight, i.p.), HOMA-IR and signs of oxidative stress in liver were evaluated in offspring at 8 weeks of age.

Females but not males, showed glucose intolerance in the GTT (Two-way ANOVA with repeated-measures: females GTT: interaction: ns, main effect treatment: p<0.05, A50 different from C. Males GTT: interaction and main effect treatment: ns). Area under the glucose curve (GTT-AUC), showed no differences in males but in females A50 differed from C (Two-way ANOVA: interaction: p<0.05, A50 female different from C female). HOMA-IR index (HOMA-IR= Fasting insulin (μU/ml) x Fasting glucose (mmol/L) / 22.5) was altered in both males and females; A50 females showed an increased HOMA-IR index compared to Controls, indicating some degree of insulin resistance, A50 males presented decreased HOMA-IR index, showing increased insulin sensitivity (Two-way ANOVA: interaction: p<0.05. A50 female different from C female, p<0.05, A50 male different from C male, p<0.05).

Insulin secretion tended to be lower than in controls in both sexes, not reaching statistical significance. Nevertheless, when the IST-AUC was calculated a significant decrease was observed in both male and female offspring (Two-way ANOVA: interaction: ns, main effect sex: ns, main effect treatment: p<0.05; A50 different from C).

When evaluating oxidative stress parameters in livers, we found that in A50 females lipid peroxidation and GSH content were increased (One-way ANOVA: TBARS: p<0.05. A50 different from C p<0.05. GSH: p<0.05. A50 different from C, p<0.05); while Catalase Activity was not altered. No alterations were observed in livers from males in any of the parameters evaluated (One-way ANOVA: ns for each)

A50 female offspring, but not males, showed glucose intolerance in the GTT while insulin secretion (AUC) was significantly impaired in both male and female A50 offspring. Regarding insulin sensitivity, while HOMA-IR was increased in A50 females, it was decreased in A50 males compared to their respective controls. The increased insulin sensitivity in males may be the cause of lack of GTT alteration even in the presence of diminished insulin secretion, suggesting that females are more sensitive to arsenite deleterious effects than males. In agreement with this hypothesis, oxidative stress parameters were found altered in females but not in males.

 

Nothing to Disclose: MMB, NB, MB, CV, CC, CL, VAL