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Abstract DM is a chronic metabolic defect characterized by hyperglycemia, affecting metabolism of carbohydrates, fats, and proteins due to deficiencies in insulin releasing or efficacy (Shaik et al., 2022). Cognition is the rational process of information acquisition and recognition through thought, feeling, practice, and proficiency (Damanik and Yunir, 2021). T2DM may be associated with impaired cognitive function such as problem solving, planning, organization, insight, reasoning as well as intentions (Lam et al., 2014). Janumet ® Film-coated tablets are available for oral administration in strengths of 1000 mg and 50 mg of metformin hydrochloride and sitagliptin phosphate respectively (Schnaars et al., 2023). The present work aims to study and compare the possible effect of glycemic control by using insulin and janumet drugs on neurocognitive dysfunctions in experimentally-induced T2DM in rats. To achieve this aim, fifty adult male albino rats of a local strain were used in this study, rats were equally divided into the following experimental five groups (10 rats each) following seven days of aclimatization: (1) Normal non-treated group (Control). (2) Control janumet-treated group (Janumet), taking 4ml /kg/day of janumet via oesophageal gavage for 4 weeks. (3) Diabetic non-treated group (Diabetic), offering them to HFD for 2 weeks followed by I.P injection of STZ in a dose of 35mg/Kg. B.W. (4) Diabetic insulin-treated group (Diabetic+ Insulin), taking10-20 IU/kg of insulin according to their FBG. (5) Diabetic janumet-treated group (Diabetic+ Janumet), taking Janumet as in Janumet group. After treatment, rats were subjected to assessment the spatial memory and learning by using Morris water maze and Y-maze tests and then retro orbital blood samples were collected to measure the glycemic state markers (FBG, HbA1C, serum insulin and HOMA-IR), lipid profile markers (serum cholesterol, serum triglycerides and serum HDL) and serum TAC level. After which, rats were sacrified by cervical dislocation, their brains were extracted and each brain was divided into 2 equal halves. The right half was weighed and prepared for tissue homogenization for estimation of the anti-oxidant activity of the enzyme SOD, lipid peroxidation marker (MDA), TNF-𝛼 and IL-1B. The left half will be fixed in 10% formalin saline for histopathological study of the hippocampal tissue using H&E stain. In the present study, the diabetic non-treated group showed significant elevations in FBG, HbA1C, HOMA-IR, serum cholesterol, serum triglyceride, MDA, TNF-α and IL-1B associated with significant reductions in serum insulin, serum HDL, serum TAC, SOD and impairment of the neurobehavioral tests when compared with the corresponding values in the control janumet-treated group and normal non-treated group. Diabetic insulin-treated group and diabetic janumet-treated group revealed significant reductions in FBG, HbA1C, HOMA-IR, serum cholesterol, serum triglyceride, MDA, TNF-α and IL-1B associated with significant elevations in serum insulin, serum HDL, serum TAC, SOD and improvement of the neurobehavioral tests when compared with the corresponding values in the diabetic non-treated group. |