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COMPARISON OF METABOLIC PROFILE, CHARACTERISTICS OF HIPPOCAMPAL MUSCARINIC RECEPTORS AND FUNCTIONALITY OF LANGERHANS ISLETS UNDER EFFECTS OF EXENATIDE IN EXPERIMENTAL MODELS OF DIABETES MELLITUS AND OBESITY IN RATS.
Metabolic syndrome is close related to diabetes mellitus type 2, obesity and neurodegenerative processes, being a serious public health problem. In turn, muscarinic receptors in the hippocampus participate decisively in the modulation of cognitive functions, learning and memory, which are compromised in neurodegenerative processes. Among the most recent pharmacological resources for diabetes mellitus type 2 there is the exenatide, which was developed from a peptide isolated from the Gila monster (Heloderma suspectum) venom and presenting agonism on glucagon-like peptide-1 hormone receptor and resistance to the hydrolysis by dipeptidyl-peptidase IV. There are also some evidences that this drug can be effective to reduce food intake and body weight and to ameliorate learning and memory performance. However, its differential actions on the metabolic profile are not fully characterized and no data exist about its influence on muscarinic receptors in animal models of diabetes mellitus type 2 and obesity induced by excitotoxicity and hypercaloric diet. This characterization would contribute to discover new mechanisms related to the etiology of obesity and to the prevention and treatment of diabetes mellitus and neurodegenerative processes in human patients. For these purposes, the present project will compare these models regarding to the postsynaptic mechanisms (affinity, density and subtypes) of muscarinic receptors in the hippocampus, insulin and glucagon secretion ability and viability of isolated Langerhans islets, food and water intake, body temperature, locomotor activity, naso-anal length, body mass and adiposity, as well as hematocrit and levels of glycated hemoglobin in the blood, and osmolality, triglycerides, cholesterol (total, HDL, LDL and VLDL), glucose, C-reactive protein and total protein in the plasma, and regarding the effects of exenatide on all these parameters. (AU)
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