Evaluation of Diabetogenic Mechanism of High Fat Diet in Combination with Arsenic Exposure in Male Mice

Document Type: Research article

Authors

1 Health Research Institute, Diabetes Research Center, Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

2 Department of Pharmacology, School of Medicine, Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

3 Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

4 Department of Pharmacology and Toxicology, School of Pharmacy, Jundishapur University of Medical Sciences, Ahvaz, Iran.

5 Department of Physiology, Student Research Committee of Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran.

6 Department of Toxicology, School of Pharmacy, Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

Obesity is a main reason of type 2 diabetes and also chronic exposure to arsenic (As)
can produce diabetic symptoms. In previous studies, the association between high-fat diet
and arsenic in the incidence of diabetes was found, but the role of beta cells activity, liver
mitochondrial oxidative stress, and hepatic enzymes (leptin, adiponectin and beta amylase)
was unclear. Thus, present study was conducted to evaluate the diabetogenic mechanism of
arsenic followed by concomitant administration of high-fat diet (HFD) in male mice. In this
experimental study, the mice consumed with HFD or low-fat diet (LFD) while exposed to
As 25 or 50 ppm in drinking water for 20 weeks. At the end of experiments, hyperglycemia,
insulin resistance variables, lipid profile, hepatic enzymes, liver mitochondrial oxidative stress,
islet insulin secretion, liver, and pancreas histopathology were evaluated in all mice by their
own methods. Control HFD fed mice showed a significant increase in FBG, OGTT, HOMAIR,
ITT, lipid profile, leptin, β-amylase, liver mitochondrial oxidative stress, hepatic enzymes
and decreased FPI, HOMA-β, adiponectin, and islet insulin secretion or content. However,
exposure to HFD concomitant with Arsenic revealed an impressive reduction in FBG, FPI,
HOMA-IR, HOMA-β, ITT, lipid profile, and islet insulin secretion or content. This exposure
enhanced OGTT, leptin, adiponectin, liver mitochondrial oxidative stress, and hepatic enzymes.
In conclusion, HFD and arsenic concomitant administration induced impairment of OGTT and
islet insulin secretion or content through the mitochondrial oxidative stress.

Keywords

Main Subjects