Biochemical and molecular evidence on the role of vaspin in early detection of the insulin resistance in a rat model of high-fat diet and use of diazinon

Toxicology. 2019 Jan 1:411:1-14. doi: 10.1016/j.tox.2018.10.014. Epub 2018 Oct 22.

Abstract

Vaspin, as a newly discovered adipocytokine, can modulate obesity with insulin-sensitizing effects. This study mainly focused on the plasma level of vaspin in insulin resistant rats, which received high-fat diet (HFD) and diazinon (DZN) (70 mg/kg). Upon 30-day experiment, related oxidative stress and inflammatory markers of plasma, the toxic effects of DZN and HFD on the histological structure of the liver, as well as the expression levels of potential genes associated with insulin resistance, phosphatase and tensin homolog (PTEN) and Forkhead box protein O1 (FoxO1) were evaluated. Metabolic parameters implicated to the glucose and insulin statues such as homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT) and fasting blood glucose (FBG) were determined. DZN significantly inhibited almost 50% of the plasma cholinesterase (ChE) activity. A remarkable increase of MDA level was observed in groups that received DZN and DZN + HFD. Animals treated with DZN or DZN + HFD showed significant changes in reactive oxygen species (ROS) level. The level of plasma tumor Necrosis Factor alpha (TNF-α) was noticeably elevated in the exposed groups. The highest elevation in vaspin level was observed in HFD group followed by DZN treated animals. In all treated groups, insulin level significantly increased and also, the area under the curve (AUC0-180) values of plasma glucose heightened considerably. The histopathological micrographs of HFD + DZN treated group indicated a severe fatty change. The plasma concentration of DZN was significantly higher in the DZN-treated group in comparison to the DZN + HFD group. FoxO1 and PTEN mRNA levels were significantly overexpressed in the DZN and HFD exposed groups. In HFD treated group, PTEN expression significantly increased compared with the DZN and DZN + HFD groups. Consequently, in contrast to oxidative stress and inflammatory biomarkers, vaspin level would be a more reliable diagnostic factor when it comes to the insulin resistance.

Keywords: Diazinon; FoxO1; Insulin resistance; PTEN; Toxicity; Vaspin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Cholinesterases / blood
  • Diazinon / toxicity*
  • Diet, High-Fat / adverse effects*
  • Early Diagnosis
  • Glucose Tolerance Test
  • Insecticides / toxicity*
  • Insulin Resistance*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Nerve Tissue Proteins
  • Oxidative Stress / drug effects
  • PTEN Phosphohydrolase / biosynthesis
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Serpins / blood*

Substances

  • Blood Glucose
  • Insecticides
  • Nerve Tissue Proteins
  • Reactive Oxygen Species
  • Serpina12 protein, rat
  • Serpins
  • Foxo1 protein, rat
  • Cholinesterases
  • PTEN Phosphohydrolase
  • Pten protein, rat
  • Diazinon