title: Molecular and immunohistochemical effects of metformin in a rat model of type 2 diabetes mellitus.
abstract: Type 2 diabetes mellitus (T2DM) is a serious health issue worldwide. The disease is characterized by insulin resistance (IR), which leads to dyslipidemia and alterations in the expression levels of a number of genes. Metformin is the standard treatment for T2DM; however, the exact mechanism underlying metformin regulation is not fully understood. The aim of the present study was to investigate the effects of metformin on serum lipid profiles and the expression levels of various genes that are associated with IR, as well as the histopathological changes in the liver and pancreas. A T2DM rat model was established by feeding the rats a high-fat diet for 4 weeks, combined with a dose of streptozotocin (35 mg/kg body weight). Following the successful induction of T2DM, metformin was administered orally (400 mg/kg/day) for 4 weeks. The results indicated that metformin improved the symptoms of IR by normalizing the serum lipid profiles in the diabetic rats. Furthermore, metformin upregulated the expression of insulin receptors and genes associated with lipid metabolism, including acyl-CoA oxidase, carnitine palmitoyl transferase-1 and peroxisome proliferator activated receptor-α. In addition, treatment with metformin downregulated the expression levels of fetuin-A and retinol binding protein-4 (RBP-4), while normalizing the expression of perilipin that had been reduced in the T2DM rats. Metformin administration induced regenerative changes in the hepatocyte cytoplasm and parenchyma. In the pancreas, treatment with metformin was shown to induce positive signaling for insulin and the regeneration of pancreatic β cells. In summary, metformin treatment ameliorated a number of the harmful effects associated with T2DM via the modulation of the expression levels of fetuin-A, RBP-4, perilipin and various genes associated with lipid metabolism, resulting in regenerative changes in the liver and pancreatic cells.
authors.affiliation: Medical Laboratory Department, Faculty of Applied Medical Sciences, Taif University, Taif, Mecca 21995, Saudi Arabia ; Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Sharqia 44519, Egypt.
authors.forename: Tamer Ahmed
authors.initials: TA
authors.lastname: Ismail
authors.affiliation: Medical Laboratory Department, Faculty of Applied Medical Sciences, Taif University, Taif, Mecca 21995, Saudi Arabia ; Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, Benha, Al Qalyubia 13736, Egypt.
authors.forename: Mohamed Mohamed
authors.initials: MM
authors.lastname: Soliman
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Sharqia 44519, Egypt.
authors.forename: Mohamed Abdo
authors.initials: MA
authors.lastname: Nassan
keywords: fetuin-A; immunohistochemistry; mRNA expression; metformin; perilipin; type 2 diabetes