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The daily rhythm of glucose metabolism is governed by the circadian clock, which consists of cell-autonomous clock machineries residing in nearly every tissue in the body. Disruption of these clock machineries either environmentally or genetically induces the dysregulation of glucose metabolism. Although the roles of clock machineries in the regulation of glucose metabolism have been uncovered in major metabolic tissues, such as the pancreas, liver, and skeletal muscle, it remains unknown whether clock function in non-major metabolic tissues also affects systemic glucose metabolism. Here, we tested the hypothesis that disruption of the clock machinery in the heart might also affect systemic glucose metabolism, because heart function is known to be associated with glucose tolerance. We examined glucose and insulin tolerance as well as heart phenotypes in mice with heart-specific deletion of Bmal1, a core clock gene. Bmal1 deletion in the heart not only decreased heart function but also led to systemic insulin resistance. Moreover, hyperglycemia was induced with age. Furthermore, heart-specific Bmal1-deficient mice exhibited decreased insulin-induced phosphorylation of Akt in the liver, thus indicating that Bmal1 deletion in the heart causes hepatic insulin resistance. Our findings revealed an unexpected effect of the function of clock machinery in a non-major metabolic tissue, the heart, on systemic glucose metabolism in mammals.

The crisis in Asia which started in 1997 has changed its name, from a currency crisis to a financial and then an economic crisis and finally the Asian crisis. Some say that the virtual integration through trade and investment flows in the APEC region turned out to work negatively in disseminating currency and/or economic turmoil. In the European Union, by contrast, the new unified currency started to circulate and its monetary integration appeared to reach the final stage, where virtual as well as formal integration through trade and investment has been realised over the past decades. It remains to be seen, however, whether this macroeconomic integration with one monetary and multiple fiscal authorities will work well or not.