{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:51:52Z","timestamp":1781657512412,"version":"3.54.5"},"reference-count":40,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01-DK098517"],"award-info":[{"award-number":["R01-DK098517"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Beckwith\u2013Wiedemann Syndrome (BWS) is an overgrowth syndrome caused by various genetic or epigenetic abnormalities in a cluster of imprinted genes on chromosome 11p15. Congenital hyperinsulinism (HI) is one of the cardinal features of BWS, but the pathophysiology of HI in BWS has not been clearly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We describe the islet phenotype of a series of infants with severe HI and comorbid BWS who required pancreatectomy for intractable hypoglycemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The cases are a subset of HI patients who required pancreatectomy and had Beckwith\u2013Wiedemann Syndrome. Molecular testing for BWS was performed by SNP array and chromosome 11p15 methylation analysis. Functional analysis of insulin secretion in pancreatic islets isolated from pancreatectomy samples was completed with perifusion experiments and cytosolic Ca2+ measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Similar to what we had previously described in islets isolated from the pancreas of infants with HI due to inactivating mutations in the KATP channel, BWS\u2013HI islets have elevated concentrations of cytosolic calcium and secrete insulin in response to stimulation with a physiologic mixture of amino acids. However, unlike KATPHI islets, most BWS\u2013HI islets retain responsiveness to stimulation with glucose and the KATP channel inhibitor glyburide. Through RNAseq analysis, we observed that expression of KCNQ1, encoding the pore-forming subunit of a voltage-gated K + channel (Kv7.1), is reduced in BWS\u2013HI islets compared to normal human islets (3-fold; P = 4.5 \u00d7 10-7).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our expression analysis and functional evaluation of islets isolated from BWS\u2013HI patients reveal the spectrum of insulin secretion responses found across BWS etiologies and suggest a potential role for loss of KCNQ1 expression in the complex pathophysiology responsible for the hyperinsulinism in BWS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag050","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T12:50:19Z","timestamp":1770382219000},"page":"1874-1885","source":"Crossref","is-referenced-by-count":0,"title":["Functional evaluation of 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