Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood. In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells. It increased AMP-activated protein kinase (AMPK) phosphorylation and the inhibition of AMPK blocked glucose uptake. It also increased reactive oxygen species (ROS) generation. N-acetyl cysteine, a ROS scavenger, blocked irisin-induced AMPK phosphorylation. Moreover, irisin activated p38 MAPK in an AMPK-dependent manner. The inhibition and knockdown of p38 MAPK blocked irisin-induced glucose uptake. A colorimetric absorbance assay showed that irisin stimulated the translocation of glucose transporter type 4 to the plasma membrane and that this effect was suppressed in cells pretreated with a p38 MAPK inhibitor or p38 MAPK small interfering RNA. In primary cultured myoblast cells, irisin increased the concentration of intracellular calcium. STO-609, a calcium/calmodulin-dependent protein kinase kinase inhibitor, blocked irisin-induced AMPK phosphorylation, implying that calcium is involved in irisin-mediated signaling. Our results suggest that irisin plays an important role in glucose metabolism via the ROS-mediated AMPK pathway in skeletal muscle cells.

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Aims Heavy consumption of alcohol is a known risk factor for new-onset atrial fibrillation (AF). We aimed to evaluate the relative importance of frequent drinking vs. binge drinking. Methods and results A total of 9 776 956 patients without AF who participated in a national health check-up programme were included in the analysis. The influence of drinking frequency (day per week), alcohol consumption per drinking session (grams per session), and alcohol consumption per week were studied. Compared with patients who drink twice per week (reference group), patients who drink once per week showed the lowest risk [hazard ratio (HR) 0.933, 95% confidence interval (CI) 0.916–0.950] and those who drink everyday had the highest risk for new-onset AF (HR 1.412, 95% CI 1.373–1.453), respectively. However, the amount of alcohol intake per drinking session did not present any clear association with new-onset AF. Regardless of whether weekly alcohol intake exceeded 210 g, the frequency of drinking was significantly associated with the risk of new-onset AF. In contrast, when patients were stratified by weekly alcohol intake (210 g per week), those who drink large amounts of alcohol per drinking session showed a lower risk of new-onset AF. Conclusion Frequent drinking and amount of alcohol consumption per week were significant risk factors for new-onset AF, whereas the amount of alcohol consumed per each drinking session was not an independent risk factor. Avoiding the habit of consuming a low but frequent amount of alcohol might therefore be important to prevent AF.

A higher PVC burden (>26%/day) and the presence of retrograde P-waves were independently associated with PVC-mediated LV dysfunction.

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