OBJECTIVES: Sub-chronic exposures to chlorpyrifos, an organophosphorus pesticide is associated with incidence of diabetes mellitus. Biochemical basis of chlorpyrifos-induced diabetes mellitus is not known. Hence, effect of its sub-toxic exposure on redox sensitive kinases, insulin signaling and insulin-induced glucose uptake were assessed in rat muscle cell line. METHODS: In an in vitro study, rat myoblasts (L6) cell line were differentiated to myotubes and then were exposed to sub-toxic concentrations (6 mg/L and 12 mg/L) of chlorpyrifos for 18 h. Then total anti-oxidant level in myotubes was measured and insulin-stimulated glucose uptake was assayed. Assessment of activation of NFκB & p38MAPK and insulin signaling following insulin stimulation from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were done in myotubes after chlorpyrifos exposure by western blot (WB) and compared with those in vehicle-treated controls. RESULTS: The glucose uptake and total antioxidant level in L6-derived myotubes after sub-toxic exposure to chlorpyrifos were decreased in a dose-dependent manner. As measured from band density of WB, phosphorylation levels increased for redo-sensitive kinases (p38MAPK and IκBα component of NFκB) and decreased for IRS-1 (at tyrosine 1222) and Akt (at serine 473) on insulin stimulation following chlorpyrifos exposure as compared to those in controls. CONCLUSION: We conclude that sub-toxic chlorpyrifos exposure induces oxidative stress in muscle cells activating redox sensitive kinases that impairs insulin signaling and thereby insulin-stimulated glucose uptake in muscle cells. This probably explains the biochemical basis of chlorpyrifos-induced insulin resistance state and diabetes mellitus.
OBJECTIVES: Sub-chronic exposures to chlorpyrifos, an organophosphorus pesticide is associated with incidence of diabetes mellitus. Biochemical basis of chlorpyrifos-induced diabetes mellitus is not known. Hence, effect of its sub-toxic exposure on redox sensitive kinases, insulin signaling and insulin-induced glucose uptake were assessed in rat muscle cell line. METHODS: In an in vitro study, rat myoblasts (L6) cell line were differentiated to myotubes and then were exposed to sub-toxic concentrations (6 mg/L and 12 mg/L) of chlorpyrifos for 18 h. Then total anti-oxidant level in myotubes was measured and insulin-stimulated glucose uptake was assayed. Assessment of activation of NFκB & p38MAPK and insulin signaling following insulin stimulation from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were done in myotubes after chlorpyrifos exposure by western blot (WB) and compared with those in vehicle-treated controls. RESULTS: The glucose uptake and total antioxidant level in L6-derived myotubes after sub-toxic exposure to chlorpyrifos were decreased in a dose-dependent manner. As measured from band density of WB, phosphorylation levels increased for redo-sensitive kinases (p38MAPK and IκBα component of NFκB) and decreased for IRS-1 (at tyrosine 1222) and Akt (at serine 473) on insulin stimulation following chlorpyrifos exposure as compared to those in controls. CONCLUSION: We conclude that sub-toxic chlorpyrifos exposure induces oxidative stress in muscle cells activating redox sensitive kinases that impairs insulin signaling and thereby insulin-stimulated glucose uptake in muscle cells. This probably explains the biochemical basis of chlorpyrifos-induced insulin resistance state and diabetes mellitus.
Authors: G Chiapella; J Flores-Martín; M E Ridano; L Reyna; G Magnarelli de Potas; G M Panzetta-Dutari; S Genti-Raimondi Journal: Placenta Date: 2013-07-11 Impact factor: 3.481
Authors: Pedro Posadas-Rodríguez; Natalia Esmeralda Posadas-Rodríguez; Viridiana Yazmín González-Puertos; Rafael Toledo-Pérez; José Luis Ventura-Gallegos; Alejandro Zentella; Luis Enrique Gómez-Quiroz; Mina Königsberg; Armando Luna-López Journal: Oxid Med Cell Longev Date: 2020-05-16 Impact factor: 6.543