Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Until the Sui Dynasty in China, night sweat and spontaneous perspiration had been thought to be caused by same pathophysiology, that is, lowered superficial resistance by deficiency of Qi.In the Tang Dynasty, these were considered to have different pathophysiologies and a new principle indicated that pathogenic heat caused night sweat.In the Song and Jing Dynasties, deficiency of blood and pathogenic heat by deficiency of Yin was also considered to cause night sweat.In the Jing Dynasty, exogenous pathogens, such as Cold were considered to cause night sweat, which indicated the principle that not only the deficiency syndrome but also the excess syndrome caused night sweat.In the beginning of the Yuan and Ming Dynasties, it was concluded that the deficiency of Yin caused night sweat and the deficiency of Yang caused spontaneous perspiration.In the middle of the Ming Dynasty, another new theory indicated that deficiency of Yang also possibly caused night sweat; therefore we should diagnose abnormal sweat depending on the pathophysiology in each case.In the Qing Dynasty, new theories were established stating that not only exogenous pathogens but also Damp-heat, undigested food and stagnation of blood, all of which are included in excess syndrome, cause night sweat, and that based on which part of the body sweats occurred we might understand pathophysiology of night sweat. The night sweat by Warm-heat, which is different from the one by Wind-cold, was considered to be caused with deficiency of Yin.Thus we conclude that the theories of night sweat developed over time, based on Chinese medical classics.