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.Analysis of Disaster Prescriptions Received at a Pharmacy after the Kumamoto Earthquake
Eriko ANAMI ; Toyonobu SAKAMOTO ; Yuko ISOO ; Tomoharu TOKUYAMA ; Kenji TSUKAMOTO ; Akiko OKITSU ; Tomoko AMAGATA ; Ichiro INABA ; Yasuaki MIYANO ; Hiroyuki KIDO ; Eiji YUKAWA
Japanese Journal of Drug Informatics 2021;23(3):135-142
Objective: Soon after two massive earthquakes in Kumamoto, Japan, on April 14 and 16, 2016, the Shirakawasuigen pharmacy located in the Minamiaso village received prescriptions for disaster medications. Since prescriptions for disaster medications are typically used at temporary emergency shelters, pharmacies usually do not receive requests for them. On checking the content of these prescriptions, we found numerous prescription errors and queries. This study aimed to assess issues with dispensing medications after disasters.Methods: We reviewed all disaster medication prescriptions received by the pharmacy from April 20 to May 28, 2016 and the medication histories of these patients. We confirmed each patient’s data and medical and medication histories. Furthermore, we classified disaster prescription errors and queries into five categories according to their content and summed them in each category.Results: We obtained patients’ medical and medication histories from 100 (77.5%) of the 129 prescriptions received. Of the 129 prescriptions, a total of 158 prescription errors and queries pertaining to 96 (74.4%) prescriptions were confirmed: 88 (55.7%) for unclear medication usage and dosages, 22 (13.9%) for incorrect medication names, 34 (21.5%) for pharmaceutical queries, 8 (5.1%) for exceeding fixed prescription days (within seven days), and 6 (3.8%) for other issues.Conclusion: Nearly 80% of the prescriptions for disaster medications had prescription errors and queries. Therefore, we evaluated that the prescription’s format and entry method can be improved. Furthermore, to ensure a smooth drug supply and to reduce prescription entry deficiencies and formal prescription queries, pharmacists need to effectively manage disaster prescriptions.
3.Survey on the Number of Pharmacies Storaged Sennoside Generic Products and Patient Preference for Their Selection
Ichiro INABA ; Kayoko OHURA ; Yuichiro NAKADA ; Teruko IMAI
Japanese Journal of Drug Informatics 2019;21(1):1-8
Objective: The use of generic products is a solution to the increasing healthcare cost in Japan. The pharmaceutical companies are trying to develop several generic products suitable to patient’s taste. The contribution of pharmacist by selecting generic product to each patient and a collection of patient’s opinion for products may accelerate the development of generic products improved usability for patients and medical workers. The present study examined the storage of generic products of sennoside in pharmacies and the patient preference for selection of generic products in 2003 and 2016 in Kumamoto, Japan.Methods: Sennoside was selected as a model drug, since it developed several generic products for long period. The survey on storage of sennoside pharmaceutics and the questionnaire survey for its generic products to patients were conducted at ethical pharmacies. The appearance and the dissolution of sennoside from generic tablets were compared with original product, Pursennid.Results: Thirteen sennoside products were stored in 2003 and 2016. The number of pharmacies that stored generic products increased from 33 to 54% in 13 years. The largest number of patients preferred Pursennid in 2003. In contrast, two generic products were more preferred than Pursennid in 2016. Interestingly, the reasons for preferring products were almost the same between 2003 and 2016, and their majority was color and size of tablet. The generic products tend to have a thinner thickness and larger diameter than Pursennid. The most preferred generic product in 2016 showed a faster dissolution of sennoside than Pursennid. However, the use of generic products is mainly related to their tablet appearances due to unrelation between the pharmacological effect of sennoside and its dissolution in GI tract.Conclusion: In the development of generic products of sennoside, as well as quality, the appearance is an important factor.


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