GLUT1欠損症の個別化治療に新たな可能性 －モデルマウスの網羅的表現型解析により糖代謝の性差を発見－

2026-09-29 理化学研究所

GLUT1欠損症モデルマウスにおけるインスリン動態の変化を発見

＜関連情報＞

• https://www.riken.jp/press/2026/20260929_3/index.html
• https://journals.biologists.com/dmm/article/19/9/dmm052836/372967/Female-specific-alterations-in-insulin-dynamics

Glut1DSマウスモデルにおけるインスリン動態の雌特異的な変化は、耐糖能異常と関連している Female-specific alterations in insulin dynamics are associated with glucose tolerance in a Glut1DS mouse model

amio Furuse,Tomoko Kushida,Akiko Shinogi,Mao Ozaki,Ryoko Yanagisawa,Masaru Tamura
Disease Models & Mechanisms  Published:21 September 2026
DOI:https://doi.org/10.1242/dmm.052836

ABSTRACT

Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare autosomal dominant genetic disorder caused by mutations in SLC2A1, which results in impaired glucose transport across the blood−brain barrier. Patients with Glut1DS present with various symptoms, including seizures, delayed development and movement disorders. The current first-line therapy − ketogenic diet − has shown variable efficacy, highlighting the need to explore alternative therapeutic strategies. This study aimed to investigate comprehensive phenotypic characteristics of the Glut1DS mouse model B6(D2)-Slc2a1<Rgsc200>/1Rbrc to establish foundational data for identifying novel therapeutic targets. The Slc2a1^Rgsc200 mutant mouse was phenotypically characterized at the Japan Mouse Clinic of the RIKEN BioResource Research Center by using a phenotyping pipeline that included intraperitoneal glucose tolerance test (IPGTT) and clinical blood chemistry analyses. Heterozygous Glut1DS mutants exhibited no differences in basal plasma glucose or glycosylated hemoglobin A1c levels when compared to wild-type controls. However, female heterozygous mutants showed decreased glucose levels during IPGTT, accompanied by increased plasma insulin levels following glucose administration. These findings support recent evidence linking insulin signaling to seizure control in patients with Glut1DS, as demonstrated in human studies.