Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD ; Department of Sport Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Sleep. 2013 Oct 1;36(10):1483-90; 1490A-1490B. doi: 10.5665/sleep.3040.
Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued.
C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed.
Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted.
Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism.
阻塞性睡眠呼吸暂停与胰岛素抵抗、葡萄糖耐量受损和 2 型糖尿病有关。尽管有几项研究表明，阻塞性睡眠呼吸暂停中的间歇性低氧可能导致葡萄糖稳态异常，但仍需确定停止暴露后这些异常是否会改善。本研究旨在描述间歇性低氧对葡萄糖稳态、β细胞功能和肝葡萄糖代谢的影响，并探讨在停止低氧暴露后这些损伤是否会改善。
C57BL6/J 小鼠接受 14 天间歇性低氧、14 天间歇性空气或 7 天间歇性低氧后再进行 7 天间歇性空气（恢复范式）暴露。进行葡萄糖和胰岛素耐量试验以评估全身胰岛素敏感性并计算β细胞功能的指标。还评估了胰腺组织中的氧化应激和分离肝细胞中的葡萄糖输出。
间歇性低氧使空腹血糖水平升高，并使葡萄糖耐量分别恶化 67%和 27%。此外，间歇性低氧暴露与胰岛素敏感性和β细胞功能受损、肝糖原增加、肝细胞葡萄糖输出增加以及胰腺氧化应激增加有关。虽然停止低氧暴露后空腹血糖水平和肝葡萄糖输出恢复正常，但葡萄糖耐量受损、胰岛素抵抗和β细胞功能受损仍持续存在。
间歇性低氧诱导胰岛素抵抗、损害β细胞功能、增强肝细胞葡萄糖输出并增加胰腺氧化应激。停止低氧暴露并不能完全逆转观察到的葡萄糖代谢变化。
