Efeitos da apneia obstrutiva do sono sobre o metabolismo de glicose: estudo em um novo modelo experimental
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Data
2012
Autores
Quadros, Caren Dal`Mora de [UNIFESP]
Orientadores
Hirata, Aparecida Emiko [UNIFESP]
Tipo
Tese de doutorado
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Resumo
Pacientes com apneia obstrutiva do sono (AOS) muitas vezes apresentam sindrome metabolica, porem os mecanismos desta associacao nao estao claros; em parte porque a presenca de comorbidades dificulta a identificacao das causas e consequencias. Investigamos se apneia afeta a sensibilidade a insulina. Usamos um balao traqueal contido em um tubo de Teflon para induzir apneia sem provocar dor traqueal no rato consciente. Uma semana apos a implantacao do balao, os ratos foram submetidos a 8 h de apneia intermitente de 14 s a cada 2 min. Ratos controles tiveram o balao traqueal, mas nao foram submetidos a apneia. Trinta minutos apos o termino das apneias, a glicose sanguinea e a insulina plasmatica estavam elevadas. O teste de tolerancia a glicose (injecao i.v. de 1 g/kg de glicose) mostrou que apneia reduziu a metabolizacao da glicose pelos tecidos. O teste de tolerancia a insulina (injecao i.v. de 0,75 U/kg de insulina) mostrou uma tendencia (p = 0,07) de decaimento da glicose mais lento apos apneia, sugerindo que apneia induziu a resistencia a insulina. A apneia aumentou a secrecao de insulina estimulada por 16,7 mM de glicose em ilhotas de Langerhans isoladas. Westerns blots nao mostraram diferencas entre ratos apneicos e ratos controles na ativacao do IR, IRS-1, IRS-2, IRS-1/PI3-K, IRS-2/PI3-K e AKT no musculo esqueletico e no figado. Em conclusao, 8 h de apneia intermitente induziu alteracoes no metabolismo de glicose. Este periodo relativamente curto nao prejudicou as etapas iniciais da via de sinalizacao insulinica
Patients with sleep apnea often have metabolic syndrome, but the mechanisms of this association are not clear, partly because the presence of comorbidities complicates the identification of causes and effects. We investigated if apnea affects the sensibility to insulin. We used a tracheal balloon contained in a Teflon tube to induce apnea without provoking tracheal pain in the conscious rat. One week after implantation of the balloon, rats were subjected to 8 h of intermittent apnea, 14 s every 2 min. Control rats had a tracheal balloon, but were not subjected to apnea. Thirty min after the end of the apneas, blood glucose and plasma insulin were increased. The glucose tolerance test (i.v. injection of 1 g/kg glucose) showed that apnea reduced the metabolism of glucose by the tissues. The insulin tolerance test (i.v. injection of 0.75 U/kg insulin) showed a trend (p=0.07) toward reduced fall of glucose levels after apnea, suggesting that apnea induced resistance to insulin. Apnea increased insulin secretion induced by 16.7 mM glucose in isolated islets of Langerhans. Westerns blots failed to show differences between rats subjected to apnea and controls in the activation of IR, IRS-1, IRS-2, IRS-1/PI3-K, IRS-2/PI3-K and AKT in skeletal muscle and liver tissue. In conclusion, 8 h of intermittent apnea induced several changes in glucose metabolism. This relatively short period did not affect the initial steps of insulin signaling pathway .
Patients with sleep apnea often have metabolic syndrome, but the mechanisms of this association are not clear, partly because the presence of comorbidities complicates the identification of causes and effects. We investigated if apnea affects the sensibility to insulin. We used a tracheal balloon contained in a Teflon tube to induce apnea without provoking tracheal pain in the conscious rat. One week after implantation of the balloon, rats were subjected to 8 h of intermittent apnea, 14 s every 2 min. Control rats had a tracheal balloon, but were not subjected to apnea. Thirty min after the end of the apneas, blood glucose and plasma insulin were increased. The glucose tolerance test (i.v. injection of 1 g/kg glucose) showed that apnea reduced the metabolism of glucose by the tissues. The insulin tolerance test (i.v. injection of 0.75 U/kg insulin) showed a trend (p=0.07) toward reduced fall of glucose levels after apnea, suggesting that apnea induced resistance to insulin. Apnea increased insulin secretion induced by 16.7 mM glucose in isolated islets of Langerhans. Westerns blots failed to show differences between rats subjected to apnea and controls in the activation of IR, IRS-1, IRS-2, IRS-1/PI3-K, IRS-2/PI3-K and AKT in skeletal muscle and liver tissue. In conclusion, 8 h of intermittent apnea induced several changes in glucose metabolism. This relatively short period did not affect the initial steps of insulin signaling pathway .
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Citação
QUADROS, Caren Dal`Mora de. Efeitos da apneia obstrutiva do sono sobre o metabolismo de glicose: estudo em um novo modelo experimental. Tese (Doutorado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2012.