Effects of acarbose on the acceleration of postprandial hyperglycemia-induced pathological changes induced by intermittent hypoxia in lean mice.

Postprandial hyperglycemia (PPH) and intermittent hypoxia related to the sleep apnea syndrome are important predictors of cardiovascular disease. We investigated the effects of intermittent hypoxia on pathological changes in the left ventricular (LV) myocardium caused by PPH in lean mice and evaluated the influence of acarbose, an α-glucosidase inhibitor. Male C57BL/6J mice aged 8 weeks were exposed to intermittent hypoxia (8 h/day during the daytime) or kept under normoxia. PPH was induced by restriction of feeding to 1-h periods twice a day, with the restricted diet (RD) mice receiving either standard chow or chow containing 0.02% acarbose. Another group of mice were fed standard chow ad libitum (AL). Plasma glucose levels after food intake were significantly elevated in RD but not in AL mice, and glucose levels were suppressed by acarbose. Intermittent hypoxia exacerbated cardiomyocyte hypertrophy and interstitial fibrosis in the LV myocardium of RD mice. Superoxide production and expression of 4-hydroxy-2-nonenal in the LV myocardium with intermittent hypoxia were increased in RD mice, but not AL mice. In addition, expression of tumor necrosis factor α (TNF-α) mRNA was increased in hypoxic RD mice. Treatment with acarbose inhibited oxidative stress and TNF-α mRNA expression and preserved the histological architecture of the LV myocardium.