Changes in glucose metabolism and reversion of genes expression in the liver of insulin-resistant rats exposed to malathion. The protective effects of N-acetylcysteine

• Malathion-treated rats showed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices.
• Malathion up-regulated liver GP, GSK3β and PEPCK mRNA expressions while, the expression of glucokinase gene is down-regulated.
• N-acetylcysteine decreased insulin resistance and ameliorated insulin sensitivity after malathion exposure.
• N-acetylcysteine supplementation restored liver GP and PEPCK expression.

Organophosphorus pesticides are known to disturb glucose homeostasis and increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on insulin signaling pathways and the protective effects of N-acetylcysteine (NAC). Malathion (200 mg/kg) and NAC (2 g/l) were administered orally to rats, during 28 consecutive days. Malathion increases plasma glucose, plasma insulin and glycated hemoglobin levels. Further, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The GP, GSK3β and PEPCK mRNA expressions were amplified by malathion while, the expression of glucokinase gene is down-regulated. On the basis of biochemical and molecular findings, it is concluded that malathion impairs glucose homeostasis through insulin resistance and insulin signaling pathways disruptions in a way to result in a reduced function of insulin into hepatocytes. Otherwise, when malathion-treated rats were compared to NAC supplemented rats, fasting glucose and insulin levels, as well as insulin resistance indices were reduced. Furthermore, NAC restored liver GP and PEPCK expression. N-acetylcysteine showed therapeutic effects against malathion-induced insulin signaling pathways disruption in liver. These data support the concept that antioxidant therapies attenuate insulin resistance and ameliorate insulin sensitivity.