1.High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction
Shun-ichiro ASAHARA ; Hiroyuki INOUE ; Yuka IHARA ; Kyoko TERUYAMA ; Asuka IMAI ; Chisako HARA ; Mizuki HARA ; Masako SEIKE ; Aisha YOKOI ; Nozomi KIDO ; Hirotaka SUZUKI ; Ayumi KANNO ; Yuka INABA ; Hitoshi WATANABE ; Go SHIOI ; Maki KIMURA-KOYANAGI ; Michihiro MATSUMOTO ; Hiroshi INOUE ; Keiichi I. NAKAYAMA ; Wataru OGAWA ; Masato KASUGA ; Yoshiaki KIDO
Diabetes & Metabolism Journal 2026;50(1):77-89
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.
2.Risk factor for difficult cases at the comprehensive consultation services about medical, welfare and legal problems
Michiki NARUSHIMA ; Chiaki ANDO ; Makoto MOCHIZUKI ; Osamu TERADA ; Hiroki SUZUKI ; Nozomi KANI ; Motoyoshi MATSUNAGA
Journal of Rural Medicine 2025;20(1):53-57
It is very important to cooperate with interprofessional personnel is in order to establish the community-based integrated care system, but this is very difficult. We have held comprehensive consultation services regarding medical, welfare, and legal problems to support the community.Objectives: This study aimed to identify the associations between background factors (such as medical conditions, intractable diseases, welfare problems, disabilities, economic difficulties, legal problems, elderly adults, children, and foreign persons) and difficult cases to provide more thorough consultation services.Patients and Methods: A survey was conducted on people who participated in comprehensive consultation services on medical, welfare, and legal issues related to medical care, welfare, and legal matters held from April 2021 to March 2024. We analyzed risk factors that may be difficult to resolve using multivariate logistic regression.Results: Multivariate analysis showed that the factor of “economic difficulty” was significantly more difficult to solve.Conclusion: When treating patients, doctors must consider the possibility of multiple underlying issues. It is advisable for doctors to be aware of the need to consult with social workers and legal professionals when necessary.
3.Replacement of SARS-CoV-2 strains with variants carrying N501Y and L452R mutations in Japan: an epidemiological surveillance assessment
Yusuke Kobayashi ; Takeshi Arashiro ; Miyako Otsuka ; Yuuki Tsuchihashi ; Takuri Takahashi ; Yuzo Arima ; Yura K. Ko ; Kanako Otani ; Masato Yamauchi ; Taro Kamigaki ; Tomoko Morita-Ishihara ; Hiromizu Takahashi ; Sana Uchikoba ; Michitsugu Shimatani ; Nozomi Takeshita ; Motoi Suzuki ; Makoto Ohnishi
Western Pacific Surveillance and Response 2022;13(3):41-50
Objective:
Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important due to concerns regarding infectivity, transmissibility, immune evasion and disease severity. We evaluated the temporal and regional replacement of previous SARS-CoV-2 variants by the emergent strains, Alpha and Delta.
Methods:
We obtained the results of polymerase chain reaction screening tests for variants conducted in multiple commercial laboratories. Assuming that all previous strains would be replaced by one variant, the new variant detection rate was estimated by fitting a logistic growth model. We estimated the transmission advantage of each new variant over the pre-existing virus strains.
Results:
The variant with the N501Y mutation was first identified in the Kinki region in early February 2021, and by early May, it had replaced more than 90% of the previous strains. The variant with the L452R mutation was first detected in the Kanto-Koshin region in mid-May, and by early August, it comprised more than 90% of the circulating strains. Compared with pre-existing strains, the variant with the N501Y mutation showed transmission advantages of 48.2% and 40.3% in the Kanto-Koshin and Kinki regions, respectively, while the variant with the L452R mutation showed transmission advantages of 60.1% and 71.9%, respectively.
Discussion
In Japan, Alpha and Delta variants displayed regional differences in the replacement timing and their relative transmission advantages. Our method is efficient in monitoring and estimating changes in the proportion of variant strains in a timely manner in each region.
4.Epidemiology of injury in a male collegiate volleyball team in Japan
Nozomi SUZUKI ; Kyoko SHIRAHATA ; Izuho ISHIMARU ; Yutaro NAKAMURA ; Hiroki UCHINO ; Masahiro OHNUMA ; Masahiro SAKURAI
Japanese Journal of Physical Fitness and Sports Medicine 2021;70(2):165-173
The purpose of this study was to examine epidemiology of injury in a male collegiate volleyball team in Japan during 2019 season. Thirty-six collegiate male volleyball players were followed during 2019 season. Injuries that required more than 24 hours to recover were classified as Time Loss (TL) injury, and those that required less than 24 hours were classified as Non-Time Loss (NTL) injury. Exposure was calculated by total number of players and hours of participation. Then, we computed injury rate per 1000 Player Hour (PH) and 1000 Athlete Exposure (AE) as outcome measures. A chi-square test was utilized to statistically compare. Eighteen injuries occurred and the overall injury rate was 1.28/1000PH and 2.05/1000AE, respectively. Of which, 11 cases were NTL injuries (0.78/1000PH, 1.26/1000AE) and 7 cases were TL injuries (0.50/1000PH, 0.80/1000AE). Within the 7 TL injuries, 5 (0.36/1000PH, 0.57/1000AE) were of minor severity. Most TL injury were classified as chronic in nature (n=5, 0.36/1000PH, 0.57/1000AE). There was no statistically significant difference between injury rate of match (n=2, 1.33/1000PH, 2.88/1000AE) and training (n=16, 1.27/1000PH, 1.98/1000AE). The most frequently injured body part in training was lower back (n=7, 0.56/1000PH, 0.87/1000AE). In match, highest injury rate was observed in ankle (n=2, 1.33/1000PH, 2.88/1000AE). In conclusion, our results showed relatively low injury rate, and majority of reported injuries were categorized as minor severity. Our study also demonstrated injury characteristics of Japanese male collegiate players that lower back injuries were prevalent in training, and acute ankle injury rate was highest in match.


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