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Acute effect of dapagliflozin SGLT-2 inhibitory on brain and hypothalamic functionality in humans and mice C57BL/6

Grant number: 14/26591-8
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2015
Effective date (End): June 30, 2017
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Bruno Geloneze Neto
Grantee:Letícia da Silva Pires
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID


Background: Co-sodium-glucose transporter type 2 (SGLT-2) is expressed in kidney and brain, including hypothalamic sites food control. The inhibition of SGLT-2 produces glycosuria and concomitant loss of calories to a decrease in body weight. However, many factors can interfere with weight loss, corresponding to expectations or not. In Brazil, Dapagliflozin is the first SGLT-2 inhibitor approved to treat type 2 diabetes by acting as oral hypoglycemic. Objectives: To study the acute effect of inhibition of SGLT-2 for Dapagliflozin in the brain and on the functionality of the hypothalamus in mice and humans. Moreover, studying the activation of NPY and POMC neurons in mice. Materials and methods: A prospective translational study with clinical intervention in mice and humans. In the first stage, 40 male mice C57BL/6 will receive Dapagliflozin intracerebroventricularly (ICV) or orally for two weeks. Respirometry, weight gain and food intake will be performed. In humans, 20 women with normal weight and normoglycemic be examined before and after administration of Dapagliflozin 10mg/day for a week. There will be anthropometry, body composition, functional magnetic resonance imaging (fMRI) and indirect calorimetry. Paired mean and correlation analyzes for comparisons between groups tests will be conducted. (AU)

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