title: 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.
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.
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: lasram_montassar@yahoo.fr.
authors.forename: Mohamed Montassar
authors.initials: MM
authors.lastname: Lasram
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
authors.forename: Narjes
authors.initials: N
authors.lastname: El-Golli
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
authors.forename: Aicha Jrad
authors.initials: AJ
authors.lastname: Lamine
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
authors.forename: Ines Bini
authors.initials: IB
authors.lastname: Douib
authors.affiliation: Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Kahena
authors.initials: K
authors.lastname: Bouzid
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
authors.forename: Alya
authors.initials: A
authors.lastname: Annabi
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: salouaelfazaa@tunet.tn.
authors.forename: Saloua
authors.initials: S
authors.lastname: El Fazaa
authors.affiliation: Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Jaouida
authors.initials: J
authors.lastname: Abdelmoula
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: najoua.gharbi@planet.tn.
authors.forename: Najoua
authors.initials: N
authors.lastname: Gharbi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D005991:Glycerol Kinase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008294:Malathion / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D005991:Glycerol Kinase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; C582554:Pck1 protein, rat; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose; D008294:Malathion; D000111:Acetylcysteine
keywords: Glucokinase; Insulin resistance; Malathion; N-acetylcysteine; PEPCK