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Effects of type 1 glucagon-like peptide hormone analogs on the fertility and dynamics of bone in obese and diabetic rats

Grant number: 14/24634-1
Support type:Regular Research Grants
Duration: June 01, 2015 - May 31, 2017
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Paulo Flávio Silveira
Grantee:Paulo Flávio Silveira
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Problem under study: Exenatide is the unique molecule derived from animal venom (Gila monster, Heloderma suspectum) that is among the most recent pharmacological resources for diabetes mellitus (DM) type 2. This drug presents agonism on glucagon-like peptide-1 hormone (GLP-1) receptor (R) and resistance to the hydrolysis by dipeptidyl-peptidase IV. There are evidences that GLP-1 and exenatide, besides acting on glycemic control, are effective to reduce food intake and body weight and to ameliorate learning and memory performance. There are also evidences about their involvement on the osseous metabolism and fertility, where their differential actions are not characterized in animal models of DM or obesity. Justification/Relevance: To improve pathophysiological knowledge about models of obesity and DM and about the comparative pharmacology and physiology of animal venoms by addressing in these models the effects of exenatide and exendin [9-39], an antagonist of GLP-1R, on fertility and bone damage. The present study will also contribute to discover new targets and ways to the prevention and treatment of infertility and bone damage as comorbities of obesity and DM. General objectives: To evaluate changes in osseous metabolism and fertility, and mainly to characterize the effects of exenatide and exendin [9-39] on these changes in the hypothalamic obesity, dietetic obesity, and DM. Methods: Hypercaloric diet for induction of dietetic obesity and neonatal administration of monossodium glutamate and streptozotocin, respectively for induction of hypothalamic obesity and DM, under treatment or not with exenatide and exendin [9-39], and healthy controls under normal diet and without any treatment. The animals will be comparatively evaluated regarding to naso-anal length, femur length, body mass, adiposity, insulin, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I), N-terminal propeptide of type 1 procollagen (P1NP), total protein in the plasma, osseous histomorphometry, and motility and sperm morphology. (AU)