Influência da grelina sobre o processo de estímulo-secreção de insulina in vitro em camundongos Swiss adultos hiperalimentados na lactação

• Ano de defesa: 2012
• Autor(a) principal: Cunha, Alessandra Cordeiro de Souza Rodrigues
• Orientador(a): Moura, Anibal Sanchez
• Banca de defesa: Trevenzoli, Isis Hara , Reis, Luis Carlos , Silva, Patrícia Cristina Lisbôa da , Carvalho, Jorge José de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Fisiopatologia Clínica e Experimental
• Departamento: Centro Biomédico::Faculdade de Ciências Médicas
• País: BR
• Palavras-chave em Português: Hipernutrição; Insulina; Grelina; Camundongos; Insulina Secreção; Hipernutrição .
• Palavras-chave em Inglês: Overfeeding; Insulin; Ghrelin; Mice
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/12639

Excess or lack of nutrients at specific times of development generates adaptive responses that can change the body causing the onset of chronic diseases in adulthood (Metabolic Programming). We studied the influence of the hormone ghrelin in insulin secretion of adult Swiss mice overfed during lactation. To induce early postnatal overnutrition, the litter size was reduced to 3 pups per litter at the 3rd day after birth. In the control group, the litter size was adjusted to 9 pups per litter. In adulthood, overfed group (OG) had an increase of 20% in body weight compared to control group (CG). OG had increased in Lee index (1705.63 g/mm + 29.3 vs 1374.10 g/mm + 54.9; p< 0.001), high body fat (31.0% + 4.6 vs 21.5% + 3.6; p< 0.01), and an elevated retroperitoneal fat (0.79 g + 0.1 vs 0.44 g + 0.1; p< 0.001), fasting hyperglycemia (151.83 mg/ dl + 8.3 vs 118.0 mg/ dl + 1.0; p< 0.001), high fasting insulinemia (54.06 µUI/ml + 2.3 vs 19.28 µUI/ml + 1.53; p< 0.001), and low fasting plasma ghrelin (98.64 pg/ml + 56.5 vs 201.14 pg/ml + 46.4; p< 0.05) compared to CG at 120 days. OG exhibited high insulin secretion in vitro at 10 minutes (209.66 µUI/ml + 46.5), 30 minutes (441.88 µUI/ml + 30.2), and 60 minutes (214.34 µUI/ml + 29.8) compared to CG, respectively 86.90 µUI/ml + 9.5; 74.31 µUI/ml + 7.7 vs 27.45 µUI/ml + 6.1; p< 0.05. Pancreatic islets from OG had a decrease of O2 consumption compared to CG (1.76 pmols O2/ s. islets-1 + 0.4 vs 4.85 pmols O2/ s. islets-1 + 1.5; p< 0.001) and an increased of GHSR1A content (3.05 % + 2.13 vs 0.95 % + 0.1; p< 0.05). Acylated ghrelin increased control group s insulin secretion in vitro at 30 minutes (CG with ghrelin: 208.50 µUI/ml + 40.85 vs CG without ghrelin 74.31 µUI/ml + 7,7; p< 0.05) and decreased the respiratory control ration (CG with ghrelin: 1.45 + 0.2 vs CG without ghrelin: 2.51 + 0.7; p< 0.05). Also acylated ghrelin increased the GLUT2 content of pancreatic islets from OG compared to CG, respectively 2.07 % + 0.5 vs 0.85 % + 0.4; p< 0.01; however acylated ghrelin was not able to stimulate insulin secretion in OG. We conclude that the overnutrition during lactation is associated with increased body fat percentage and changes in pancreatic β cells in the late stage of development. Acylated ghrelin stimulated insulin secretion only in adult CG.