{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:46:05Z","timestamp":1792788365953,"version":"4.5.0"},"reference-count":34,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"RIKEN","id":[{"id":"https:\/\/ror.org\/01sjwvz98","id-type":"ROR","asserted-by":"crossref"}]},{"name":"GLUT1 Deficiency Foundation","id":[{"id":"https:\/\/ror.org\/04a04ah29","id-type":"ROR","asserted-by":"crossref"}]},{"name":"RIKEN BRC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>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\u2212brain barrier. Patients with Glut1DS present with various symptoms, including seizures, delayed development and movement disorders. The current first-line therapy \u2212 ketogenic diet \u2212 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&amp;lt;Rgsc200&amp;gt;\/1Rbrc to establish foundational data for identifying novel therapeutic targets. The Slc2a1Rgsc200 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.<\/jats:p>","DOI":"10.1242\/dmm.052836","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:47:15Z","timestamp":1789991235000},"source":"Crossref","is-referenced-by-count":0,"title":["Female-specific alterations in insulin dynamics are associated with glucose tolerance in a Glut1DS mouse model"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-6040","authenticated-orcid":false,"given":"Tamio","family":"Furuse","sequence":"first","affiliation":[{"name":"RIKEN BioResource Research Center 1 Mouse Phenomics Division , , 3-1-1 Koyadai, Tsukuba, Ibaraki 3050074 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kushida","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Mouse Phenomics Division , , 3-1-1 Koyadai, Tsukuba, Ibaraki 3050074 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Shinogi","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Mouse Phenomics Division , , 3-1-1 Koyadai, Tsukuba, Ibaraki 3050074 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Ozaki","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Mouse Phenomics Division , , 3-1-1 Koyadai, Tsukuba, Ibaraki 3050074 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Mouse Phenomics Division , , 3-1-1 Koyadai, Tsukuba, Ibaraki 3050074 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Tamura","sequence":"additional","affiliation":[{"name":"RIKEN BioResource Research Center 1 Mouse Phenomics Division , , 3-1-1 Koyadai, Tsukuba, Ibaraki 3050074 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026092107453860100_DMM052836C1","doi-asserted-by":"publisher","first-page":"eadp1115","DOI":"10.1126\/sciadv.adp1115","article-title":"Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis","volume":"10","author":"Ardanaz","year":"2024","journal-title":"Sci. Adv."},{"key":"2026092107453860100_DMM052836C2","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1002\/glia.20375","article-title":"A quantitative overview of glucose dynamics in the gliovascular unit","volume":"55","author":"Barros","year":"2007","journal-title":"Glia"},{"key":"2026092107453860100_DMM052836C3","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.ejpn.2019.02.012","article-title":"Failure of ketogenic diet therapy in GLUT1 deficiency syndrome","volume":"23","author":"Bekker","year":"2019","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"2026092107453860100_DMM052836C4","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.seizure.2014.11.009","article-title":"Sporadic and familial glut1ds Italian patients: a wide clinical variability","volume":"24","author":"De Giorgis","year":"2015","journal-title":"Seizure"},{"key":"2026092107453860100_DMM052836C5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12263-016-0550-2","article-title":"Protein-restricted diet during pregnancy after insemination alters behavioral phenotypes of the progeny","volume":"12","author":"Furuse","year":"2017","journal-title":"Genes Nutr."},{"key":"2026092107453860100_DMM052836C6","doi-asserted-by":"publisher","first-page":"dmm038828","DOI":"10.1242\/dmm.038828","article-title":"A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain","volume":"12","author":"Furuse","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"2026092107453860100_DMM052836C7","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.ymeth.2010.12.017","article-title":"High-throughput mouse phenotyping","volume":"53","author":"Gates","year":"2011","journal-title":"Methods"},{"key":"2026092107453860100_DMM052836C8","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1001\/jamaneurol.2017.0298","article-title":"Clinical aspects of glucose transporter type 1 deficiency: information from a global registry","volume":"74","author":"Hao","year":"2017","journal-title":"JAMA Neurol"},{"key":"2026092107453860100_DMM052836C9","doi-asserted-by":"publisher","first-page":"101720","DOI":"10.1016\/j.jbc.2022.101720","article-title":"Loss of the N-acetylgalactosamine side chain of the GPI-anchor impairs bone formation and brain functions and accelerates the prion disease pathology","volume":"298","author":"Hirata","year":"2022","journal-title":"J. Biol. Chem."},{"key":"2026092107453860100_DMM052836C10","doi-asserted-by":"publisher","first-page":"42476","DOI":"10.1038\/srep42476","article-title":"CRISPR\/Cas9-mediated genome editing in wild-derived mice: generation of tamed wild-derived strains by mutation of the a (nonagouti) gene","volume":"7","author":"Hirose","year":"2017","journal-title":"Sci. Rep."},{"key":"2026092107453860100_DMM052836C11","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1111\/jdi.12829","article-title":"Sex differences in insulin and glucagon responses for glucose homeostasis in young healthy Japanese adults","volume":"9","author":"Horie","year":"2018","journal-title":"J. Diabetes Invest."},{"key":"2026092107453860100_DMM052836C12","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/ng.3360","article-title":"Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics","volume":"47","author":"Hrab\u011b De Angelis","year":"2015","journal-title":"Nat. Genet."},{"key":"2026092107453860100_DMM052836C13","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1210\/en.2019-00194","article-title":"Sex difference in corticosterone-induced insulin resistance in mice","volume":"160","author":"Kaikaew","year":"2019","journal-title":"Endocrinology"},{"key":"2026092107453860100_DMM052836C14","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1002\/epi4.12414","article-title":"Glut1 deficiency syndrome (Glut1DS): state of the art in 2020 and recommendations of the international Glut1DS study group","volume":"5","author":"Klepper","year":"2020","journal-title":"Epilepsia Open"},{"key":"2026092107453860100_DMM052836C15","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1093\/brain\/awp336","article-title":"Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder","volume":"133","author":"Leen","year":"2010","journal-title":"Brain"},{"key":"2026092107453860100_DMM052836C34","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s00415-014-7240-z","article-title":"GLUT1 deficiency syndrome into adulthood: a follow-up study","volume":"261","author":"Leen","year":"2024","journal-title":"J. Neurol."},{"key":"2026092107453860100_DMM052836C16","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1002\/acn3.51462","article-title":"Exploring diazoxide and continuous glucose monitoring as treatment for Glut1 deficiency syndrome","volume":"8","author":"Logel","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2026092107453860100_DMM052836C17","doi-asserted-by":"publisher","first-page":"6874","DOI":"10.1073\/pnas.120069197","article-title":"Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26","volume":"97","author":"Marguet","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026092107453860100_DMM052836C18","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/s41467-020-14697-z","article-title":"Pathogenic POGZ mutation causes impaired cortical development and reversible autism-like phenotypes","volume":"11","author":"Matsumura","year":"2020","journal-title":"Nat. Commun."},{"key":"2026092107453860100_DMM052836C19","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1038\/ng.3901","article-title":"Disease model discovery from 3,328 gene knockouts by the international mouse phenotyping consortium","volume":"49","author":"Meehan","year":"2017","journal-title":"Nat. Genet."},{"key":"2026092107453860100_DMM052836C20","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.cell.2018.08.019","article-title":"Mutations in disordered regions can cause disease by creating dileucine motifs","volume":"175","author":"Meyer","year":"2018","journal-title":"Cell"},{"key":"2026092107453860100_DMM052836C21","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ymgmr.2016.12.008","article-title":"Gene therapy for a mouse model of glucose transporter-1 deficiency syndrome","volume":"10","author":"Nakamura","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"2026092107453860100_DMM052836C22","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1186\/s13023-022-02513-4","article-title":"Glut1 deficiency syndrome throughout life: clinical phenotypes, intelligence, life achievements and quality of life in familial cases","volume":"17","author":"Olivotto","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"2026092107453860100_DMM052836C23","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41467-017-01995-2","article-title":"Identification of genetic elements in metabolism by high-throughput mouse phenotyping","volume":"9","author":"Rozman","year":"2018","journal-title":"Nat. Commun."},{"key":"2026092107453860100_DMM052836C24","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/414799a","article-title":"Insulin signalling and the regulation of glucose and lipid metabolism","volume":"414","author":"Saltiel","year":"2001","journal-title":"Nature"},{"key":"2026092107453860100_DMM052836C25","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/ng0298-188","article-title":"GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood\u2212brain barrier hexose carrier","volume":"18","author":"Seidner","year":"1998","journal-title":"Nat. Genet."},{"key":"2026092107453860100_DMM052836C26","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s00335-013-9482-y","article-title":"Pheno-Pub: a total support system for the publication of mouse phenotypic data on the web","volume":"24","author":"Suzuki","year":"2013","journal-title":"Mamm. Genome"},{"key":"2026092107453860100_DMM052836C27","doi-asserted-by":"publisher","first-page":"14152","DOI":"10.1038\/ncomms14152","article-title":"Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein","volume":"8","author":"Tang","year":"2017","journal-title":"Nat. Commun."},{"key":"2026092107453860100_DMM052836C28","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1002\/acn3.50881","article-title":"Therapeutic strategies for glucose transporter 1 deficiency syndrome","volume":"6","author":"Tang","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2026092107453860100_DMM052836C29","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00125-019-05040-3","article-title":"Sex differences in metabolic regulation and diabetes susceptibility","volume":"63","author":"Tramunt","year":"2020","journal-title":"Diabetologia"},{"key":"2026092107453860100_DMM052836C30","doi-asserted-by":"publisher","first-page":"11933","DOI":"10.1038\/s41598-022-16106-5","article-title":"Deficiency of protocadherin 9 leads to reduction in positive emotional behaviour","volume":"12","author":"Uemura","year":"2022","journal-title":"Sci. Rep."},{"key":"2026092107453860100_DMM052836C31","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/(SICI)1098-1136(199709)21:1&lt;2::AID-GLIA2&gt;3.0.CO;2-C","article-title":"Glucose transporter proteins in brain: Delivery of glucose to neurons and glia","volume":"21","author":"Vannucci","year":"1997","journal-title":"Glia"},{"key":"2026092107453860100_DMM052836C32","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1093\/hmg\/ddl032","article-title":"A mouse model for Glut-1 haploinsufficiency","volume":"15","author":"Wang","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"2026092107453860100_DMM052836C33","doi-asserted-by":"publisher","first-page":"585","DOI":"10.3389\/fneur.2019.00585","article-title":"Ketone bodies in neurological diseases: focus on neuroprotection and underlying mechanisms","volume":"10","author":"Yang","year":"2019","journal-title":"Front. Neurol."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052836\/3718703\/dmm052836.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052836\/3718703\/dmm052836.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:47:16Z","timestamp":1789991236000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/19\/9\/dmm052836\/372967\/Female-specific-alterations-in-insulin-dynamics"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":34,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.052836","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"article-number":"dmm052836"}}