Sublethal exposures of diazinon alters glucose homostasis in Wistar rats: Biochemical and molecular evidences of oxidative stress in adipose tissues

Abstract

Disorder of glucose homeostasis is one of the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of adipose tissue in regulating blood glucose and the role of oxidative stress in toxicity of OPs and in the continue of our previous works, in the present study we focused on tumor necrosis factor alpha (TNFα), glucose transporter type 4 (GLUT4), and nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB) in a sublethal model of toxicity by diazinon as a common OPs.Following time-course study of various doses of diazinon in impairing blood glucose, dose of 70mg/kg/day was found the optimum. Animals were treated for 4weeks and after gavage of glucose (2g/kg), the glucose change was evaluated at time-points of 0, 30, 60, 120 and 180min to identify oral glucose tolerance test (GTT). In addition, serum insulin was measured in fasting condition. In adipose tissue, oxidative stress markers including reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and TNFα were evaluated. The mRNA expression of GLUT4, Nf-κB and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were also determined by real time reverse transcription polymerase chain reaction (RT-PCR). Diazinon at dose of 70mg/kg/day impaired GTT and diminished insulin level while augmented ROS, NADPH oxidase, and TNFα. The GLUT4 mRNA expression was amplified by diazinon while unlikely, the expression of Nf-κB gene did not change.On the basis of biochemical and molecular findings, it is concluded that diazinon impairs glucose homeostasis through oxidative stress and related proinflammatory markers in a way to result in a reduced function of insulin inside adipose tissue. Although, diazinon interfered with pancreatic influence on the adipose tissue most probably via stimulation of muscarinic receptors, current data are not sufficient to introduce adipose tissue as a target organ to OPs toxicity. Considering the potential of OPs to accumulate in adipose tissue, it seems a good candidate organ for future studies. Although, hyperglycemia was not induced by diazinon but increased AUC0–180min leads us to the point that diazinon induces kind of instability in glucose homostasis and diabetes.