{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:57:12Z","timestamp":1790189832135,"version":"4.1.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":3067,"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":[[2013,5,1]]},"abstract":"<jats:p>Congenital hyperinsulinism causes persistent hypoglycemia in neonates and infants. Most often, uncontrolled insulin secretion (IS) results from a lack of functional KATP channels in all \u03b2-cells or only in \u03b2-cells within a resectable focal lesion. In more rare cases, without KATP channel mutations, hyperfunctional islets are confined within few lobules, whereas hypofunctional islets are present throughout the pancreas. They also can be cured by selective partial pancreatectomy; however, unlike those with a KATP focal lesion, they show clinical sensitivity to diazoxide. Here, we characterized in vitro IS by fragments of pathological and adjacent normal pancreas from six such cases. Responses of normal pancreas were unremarkable. In pathological region, IS was elevated at 1 mmol\/L and was further increased by 15 mmol\/L glucose. Diazoxide suppressed IS and tolbutamide antagonized the inhibition. The most conspicuous anomaly was a large stimulation of IS by 1 mmol\/L glucose. In five of six cases, immunohistochemistry revealed undue presence of low-Km hexokinase-I in \u03b2-cells of hyperfunctional islets only. In one case, an activating mutation of glucokinase (I211F) was found in pathological islets only. Both abnormalities, attributed to somatic genetic events, may account for inappropriate IS at low glucose levels by a subset of \u03b2-cells. They represent a novel cause of focal congenital hyperinsulinism.<\/jats:p>","DOI":"10.2337\/db12-1414","type":"journal-article","created":{"date-parts":[[2012,12,29]],"date-time":"2012-12-29T07:20:11Z","timestamp":1356765611000},"page":"1689-1696","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":65,"title":["Congenital Hyperinsulinism Caused by Hexokinase I Expression or Glucokinase-Activating Mutation in a Subset of \u03b2-Cells"],"prefix":"10.2337","volume":"62","author":[{"given":"Jean-Claude","family":"Henquin","sequence":"first","affiliation":[{"name":"Unit of Endocrinology and Metabolism, University of Louvain, Faculty of Medicine, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sempoux","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Louvain, Faculty of Medicine, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Marchandise","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Louvain, Faculty of Medicine, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Godecharles","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Louvain, Faculty of Medicine, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Guiot","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Louvain, Faculty of Medicine, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Nenquin","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Metabolism, University of Louvain, Faculty of Medicine, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Rahier","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Louvain, Faculty of Medicine, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,4,16]]},"reference":[{"key":"2022031303175416900_B1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ncpendmet0368","article-title":"Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates","volume":"3","author":"De Le\u00f3n","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab"},{"key":"2022031303175416900_B2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.earlhumdev.2010.05.003","article-title":"Congenital hyperinsulinism","volume":"86","author":"Arnoux","year":"2010","journal-title":"Early Hum Dev"},{"key":"2022031303175416900_B3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s10545-011-9441-2","article-title":"Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management","volume":"35","author":"Senniappan","year":"2012","journal-title":"J Inherit Metab Dis"},{"key":"2022031303175416900_B4","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1126\/science.7716548","article-title":"Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy","volume":"268","author":"Thomas","year":"1995","journal-title":"Science"},{"key":"2022031303175416900_B5","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1093\/hmg\/5.11.1809","article-title":"Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy","volume":"5","author":"Thomas","year":"1996","journal-title":"Hum Mol Genet"},{"key":"2022031303175416900_B6","first-page":"101","article-title":"Molecular biology of adenosine triphosphate-sensitive potassium channels","volume":"20","author":"Aguilar-Bryan","year":"1999","journal-title":"Endocr Rev"},{"key":"2022031303175416900_B7","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1172\/JCI25495","article-title":"ATP-sensitive potassium channelopathies: focus on insulin secretion","volume":"115","author":"Ashcroft","year":"2005","journal-title":"J Clin Invest"},{"key":"2022031303175416900_B8","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/BF00283651","article-title":"The basic structural lesion of persistent neonatal hypoglycaemia with hyperinsulinism: deficiency of pancreatic D cells or hyperactivity of B cells?","volume":"26","author":"Rahier","year":"1984","journal-title":"Diabetologia"},{"key":"2022031303175416900_B9","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1097\/00000478-198909000-00006","article-title":"Diffuse and focal nesidioblastosis. 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