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J Diabetes Metab Disord. 2018 Nov 28;17(2):325-332. doi: 10.1007/s40200-018-0379-x. eCollection 2018 Dec.

Effect of sub-toxic chlorpyrifos on redox sensitive kinases and insulin signaling in rat L6 myotubes.

Author information

1
1Department of Biochemistry, Maulana Azad Medical College, 2 Bahadur Shah Zafar Marg, New Delhi, PIN 110002 India.
2
2Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605014 India.

Abstract

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.

KEYWORDS:

Chlorpyrifos; Insulin resistance; Insulin signaling; NFκB; Type 2 diabetes mellitus; p38MAPK

Conflict of interest statement

Compliance with ethical standardsThe authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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