الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 191 |  |  |
| | | from | 191 | | |
Abstract
Type 2 Diabetes mellitus (T2DM) is a heterogeneous disorder characterized by impaired cellular responses to insulin known as insulin resistance and followed by progressive partial pancreatic β-cell dysfunction. Due to insulin resistance, pancreatic β-cells secrete abnormally high levels of insulin in order to control blood glucose levels, however overtime, hyperglycemia, hyperinsulinemia, pancreatic β-cell dysfunction and subsequent progressive pancreatic β-cell destruction occur. The aim of this study was to investigate the probable beneficial effects of protocatechuic acid (PCA), dimethyl fumarate (DMF) and cinnamaldehyde (CIN) on metabolic irregularities and vascular dysfunction in T2D rats and the possible involved mechanisms. In the present study, a rat model of T2DM was established by application of the STZ (streptozotocin) / fat / fructose fed method where Wister rats were injected with STZ (35 mg/kg, i.p.). After 30 days of feeding with HFD and 25% fructose in drinking water, protocatechuic acid (PCA) (100 mg/kg/day, orally), dimethyl fumarate (DMF) (25 mg/kg/day, orally) and cinnamaldehyde (CIN) (10 mg/kg/day, orally) were given orally from day 34 to 65.
PCA, DMF or CIN 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 and hepatic and aortic histopathological examination. Additionally, the mRNA expression of hepatic insulin signalling pathway genes and aortic nitric oxide synthase3 (eNOS) and NADPH oxidase4 (NOX4) were determined. chronic treatment with PCA, DMF and CIN significantly alleviated HFD/ fructose-induced insulin resistance as shown by decreasing AUCOGTT, AUCITT, fasting blood glucose and insulin and HOMA-IR. In addition, they increased HOMA-β index, improved lipid profile, decreased serum ALT and AST activities, serum AGE levels and aortic RAGE content. Additionally, they improved oxidative biochemical parameters, increased the mRNA expression of hepatic IRS1, PI3K-P85 subunit, AKT2 and aortic eNOS and decreased aortic NOX4 mRNA expression level. Treatment with PCA, DMF and CIN decreased steatosis, inflammation in liver of diabetic rats (score 1) and prevented the proliferation of smooth muscles of media in aortic tissue of rats.