{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:42:04Z","timestamp":1787967724132,"version":"build-2784847793"},"reference-count":18,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":2970,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the KATP channel, result in permanent neonatal diabetes mellitus. They also may cause neurologic symptoms such as mental retardation and motor problems (iDEND syndrome) and epilepsy (DEND syndrome). Sulphonylurea (SU) treatment is reported to alleviate both the neurologic symptoms and diabetes in such cases. The study aimed to establish the magnitude and functional basis of the effect of SUs on the neurologic phenotype in children with iDEND using neuroimaging before and after insulin replacement with glibenclamide.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>To localize and quantify the effect of glibenclamide administration, we performed single-photon emission computed tomography in seven patients with different mutations in KCNJ11. In five patients, measurements before and after initiation of SU treatment were performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Significant changes in single-photon emission computed tomography signal intensity after transfer to SU therapy were restricted to the cerebellum, consistent with previous data showing high Kir6.2 expression in this brain region. Cerebellar perfusion improved for both left (P = 0.006) and right (P = 0.01) hemispheres, with the mean improvement being 26.7 \u00b1 7.1% (n = 5). No patients showed deterioration of cerebellar perfusion on SU therapy. Electrophysiological studies revealed a good correlation between the magnitude of KATP channel dysfunction and the clinical phenotype; mutant channels with the greatest reduction in adenosine 5\u2032-triphosphate inhibition were associated with the most severe neurologic symptoms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>We conclude it is likely that at least some of the beneficial effects of SU treatment on neurodevelopment in iDEND patients result from improved cerebellar perfusion.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc12-2166","type":"journal-article","created":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T05:27:43Z","timestamp":1362547663000},"page":"2311-2316","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":31,"title":["Switching to Sulphonylureas in Children With iDEND Syndrome Caused by <i>KCNJ11<\/i> Mutations Results in Improved Cerebellar Perfusion"],"prefix":"10.2337","volume":"36","author":[{"given":"Wojciech","family":"Fendler","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Oncology, Haematology, and Diabetology, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Pietrzak","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Oncology, Haematology, and Diabetology, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa F.","family":"Brereton","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Lahmann","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Gadzicki","sequence":"additional","affiliation":[{"name":"Department of Radiological and Isotopic Diagnostics and Therapy, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Bienkiewicz","sequence":"additional","affiliation":[{"name":"Department of Quality Control and Radiation Protection, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Drozdz","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Oncology, Haematology, and Diabetology, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Borowiec","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Oncology, Haematology, and Diabetology, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej T.","family":"Malecki","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Collegium Medicum Jagiellonian University of Cracow, Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Ashcroft","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech M.","family":"Mlynarski","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Oncology, Haematology, and Diabetology, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,7,11]]},"reference":[{"key":"2022031222392062600_B1","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1056\/NEJMoa032922","article-title":"Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes","volume":"350","author":"Gloyn","year":"2004","journal-title":"N Engl J Med"},{"key":"2022031222392062600_B2","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/sj.ejhg.5201629","article-title":"KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features","volume":"14","author":"Gloyn","year":"2006","journal-title":"Eur J Hum Genet"},{"key":"2022031222392062600_B3","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/ncpneuro0640","article-title":"Sulfonylurea improves CNS function in a case of 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Seattle (WA): Allen Institute for Brain Science. 2009. Available from http:\/\/www.brain-map.org. 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