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.

The refill-prescription system widely implemented overseas has been discussed toward its legislation for many years but has not been enforced yet in Japan. In considering introduction of such a refill-prescription system, numerical economic effects of its introduction can be expected in this paper. Based on the survey by Kurata at al. in 2016, the first and second groups were defined for patients with prescriptions of the same medicine more than twice for 14 days or more (20.2%) and for patients in the first group who were prescribed medication for more than 180 days and visited the pharmacy over 330 days (4.4%), respectively. The number of refill-prescriptions were estimated from the total number of the prescriptions put out in 2016. In the first group 166.7 million prescriptions were replaced by refill prescription, resulting in the reduction of medical and insurance expenses by 155.6 and 108.9 billion yens, respectively, while in the second group the reduction of 36.31 million prescriptions as well as 33.9 and 23.7 billion yens for those expenses, respectively, were expected. The monthly working time of overworking doctors with poor working environment was also calculated to be shortened by 6.1〜12.1 and 1.3〜2.6 hours for these two groups, respectively. Additionally, the introduction of the refill-prescription system was estimated to reduce the physical burden of one patient by 2.7〜5.3 hours per year for consultation and waiting hours in the medical institutions. Therefore, the refill-prescription system is thought to be useful for efficient allocation of medical resources to patients.