ß-Catenin is required for optimal exercise- and contraction-stimulated skeletal muscle glucose uptake.

KEY POINTS: Loss of ß-catenin impairs in vivo and isolated muscle exercise/contraction-stimulated glucose uptake. ß-Catenin is required for exercise-induced skeletal muscle actin cytoskeleton remodelling. ß-Catenin675 phosphorylation during exercise may be intensity dependent. ABSTRACT: The conserved structural protein ß-catenin is an emerging regulator of vesicle trafficking in multiple tissues and supports insulin-stimulated glucose transporter 4 (GLUT4) translocation in skeletal muscle by facilitating cortical actin remodelling. Actin remodelling may be a convergence point between insulin and exercise/contraction-stimulated glucose uptake. Here we investigated whether ß-catenin is involved in regulating exercise/contraction-stimulated glucose uptake. We report that the muscle-specific deletion of ß-catenin induced in adult mice (BCAT-mKO) impairs both exercise- and contraction (isolated muscle)-induced glucose uptake without affecting running performance or canonical exercise signalling pathways. Furthermore, high intensity exercise in mice and contraction of myotubes and isolated muscles led to the phosphorylation of ß-cateninS675 , and this was impaired by Rac1 inhibition. Moderate intensity exercise in control and Rac1 muscle-specific knockout mice did not induce muscle ß-cateninS675 phosphorylation, suggesting exercise intensity-dependent regulation of ß-cateninS675 . Introduction of a non-phosphorylatable S675A mutant of ß-catenin into myoblasts impaired GLUT4 translocation and actin remodelling stimulated by carbachol, a Rac1 and RhoA activator. Exercise-induced increases in cross-sectional phalloidin staining (F-actin marker) of gastrocnemius muscle was impaired in muscle from BCAT-mKO mice. Collectively our findings suggest that ß-catenin is required for optimal glucose transport in muscle during exercise/contraction, potentially via facilitating actin cytoskeleton remodelling.

The change of the quantitative HBsAg level during the natural course of chronic hepatitis B.

BACKGROUND: There is insufficient information about HBsAg levels and their correlation with serum hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB). AIMS: We aimed to describe HBsAg levels during various phases of CHB and to investigate the correlation with serum HBV DNA levels. METHODS: A total of 645 treatment-naïve Korean CHB patients were included in this retrospective cross-sectional study. They were categorized into immune tolerance (IT, n=56), HBeAg-positive hepatitis (EPH, n=150), inactive carrier (IC, n=274) and HBeAg-negative hepatitis (ENH, n=165). The baseline HBsAg and HBV DNA levels were measured. RESULTS: The mean HBsAg titres (log IU/ml) differed (P<0.001): IT 4.29, EPH 3.64, IC 2.05 and ENH 3.23. In 645 patients, HBsAg and HBV DNA showed a significant correlation (r=0.693, P<0.001), and this was also observed in the IT, EPH and IC groups (r=0.664, r=0.541, r=0.505, respectively, all P<0.001), but not in the ENH group (r=0.093, P=0.321). Age had a negative correlation with HBsAg (r=-0.451, P<0.001). The cirrhotic patients had a significantly lower HBsAg level than the non-cirrhotic patients (2.41 ± 1.36 vs. 3.02 ± 1.21 log IU/ml, P<0.001). CONCLUSIONS: The HBsAg level varied significantly in different phases of CHB and was correlated with HBV DNA during the IT, EPH and IC phases. These findings can provide additional information to understand the natural course and pathogenesis of CHB.