Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Physiology

Background: Apelin, a recently identified adipokine, and its receptor (APJ) are involved in the regulation of a variety of pathphysiological processes. APJ shares marked sequence homology with angiotensin II type 1 receptor (ATR1) and both receptors are expressed in many different tissues. Objective: the purpose of the present study is to evaluate the effect of apelin treatment on obesity-induced type 2 diabetes mellitus (T2DM) and the possible interaction between apelin/APJ system and renin angiotensin system (RAS) with a particular focus on their relation with endothelial nitric oxide synthase (eNOS) pathway. Methods: forty male albino rats were divided in to 2 groups. Control group (n=8) and diabetic group (n=32). Diabetic group were further subdivided in to four groups; control diabetic group (n=8), apelin treated diabetic group (n=8), apelin+losartan treated diabetic group (n=8), apelin+L-NAME treated diabetic group (n=8). Rats in diabetic group were fed high fat high sucrose (HF-HS) diet for six weeks to induce obesity and insulin resistance (IR) + single low dose of streptozotocin (STZ, 35 mg/kg) at the end of fifth week to induce T2DM. Drugs were given from the start and continued for one week after STZ injection. Apelin-13 was given intraperitoneal (0.1omol/kg /day). Losrtan, angiotensin II type 1 receptor blocker, was given orally (30 mg/kg/day). L-NG-nitroarginine methyl ester (L-NAME), non specific eNOS inhibitor, was given intraperitoneal (10 mg/kg/day). At the end of the study body mass index (BMI) was calculated and blood samples were taken to measure serum Glucose, Insulin, Lipid profile {cholesterol, Triglycerides (TGs), High density lipoprotein (HDL), inflammatory marker: Tumor necrosis factor-Ü (TNFÜ), oxidative stress marker: Malondialdehyde (MDA), endothelial dysfunction marker: Tissue plasminogen activator (T-PA) antigen, and Nitric oxide (NO) levels. After decapitation, adipose tissue was taken for the determination of gene expression of (ATR1) and angiotensin converting enzyme 2 (ACE2)

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