Dimethylfumarate ameliorates high-fat diet/streptozotocin-induced type 2 diabetes in liver and aorta of rats

Marwa E. Abdelmageed; George S. Shehatou; Ghada M. Suddek; Hatem A. Salem

Authors

Marwa E. Abdelmageed Pharmacology and Toxicology department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
George S. Shehatou Pharmacology and Toxicology department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
Ghada M. Suddek Pharmacology and Toxicology department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
Hatem A. Salem Pharmacology and Toxicology department, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt

Keywords:

Type 2 diabetes, dimethylfumarate, oxidative stress, streptozotocin, high fat diet, advanced glycation end products, insulin signalling pathway

Abstract

In the current study, the possible curative effects of dimethylfumarate (DMF) on high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced type 2 diabetes in rats were evaluated.

Methods: T2DM was induced by feeding rats with HFD/25% fructose solution for 30 days followed by STZ (35mg/kg, i.p.), DMF effects were investigated on fasting blood glucose, insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), liver biomarkers, lipid profile, oxidative stress biomarkers, serum advanced glycation end products (AGEs) and its receptors (RAGE) in aorta. Additionally, the mRNA expression of hepatic insulin signalling pathway genes and aortic nitric oxide synthase3 (eNOS) and NADPH oxidase4 (NOX4) were determined.

Results: Treatment with DMF for 30 days decreased fasting glucose, ameliorated insulin resistance, improved lipid profile, decreased liver enzymes activities in serum, reduced serum AGEs and aortic RAGE contents, decreased malondialdehyde content, increased superoxide dismutase activity in liver and aorta and increased the reduced glutathione content in liver. Additionally, the mRNA expression of hepatic insulin signalling pathway genes and aortic eNOS was elevated and the mRNA expression of NOX4 was decreased as a result of DMF treatment.

Conclusion: Our study demonstrated that DMF possess the potential ability to ameliorate type 2 diabetes in rats.