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Gen Comp Endocrinol. 2015 May 1;215:88-97. doi: 10.1016/j.ygcen.2014.10.002. Epub 2014 Oct 18.

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.

Author information

1
Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: lasram_montassar@yahoo.fr.
2
Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
3
Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia.
4
Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: salouaelfazaa@tunet.tn.
5
Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: najoua.gharbi@planet.tn.

Abstract

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.

KEYWORDS:

Glucokinase; Insulin resistance; Malathion; N-acetylcysteine; PEPCK

PMID:
25449180
DOI:
10.1016/j.ygcen.2014.10.002
[Indexed for MEDLINE]

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