{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:30:29Z","timestamp":1773307829585,"version":"3.50.1"},"reference-count":44,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":3636,"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":[[2011,10,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Neonatal diabetes mellitus (NDM) can be caused by gain-of-function ATP-sensitive K+ (KATP) channel mutations. This realization has led to sulfonylurea therapy replacing insulin injections in many patients. In a murine model of KATP-dependent NDM, hyperglycemia and consequent loss of \u03b2-cells are both avoided by chronic sulfonylurea treatment. Interestingly, KATP mutations may underlie remitting-relapsing, transient, or permanent forms of the disease in different patients, but the reason for the different outcomes is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>To gain further insight into disease progression and outcome, we examined the effects of very early intervention by injecting NDM mice with high-dose glibenclamide for only 6 days, at the beginning of disease onset, then after the subsequent progression with measurements of blood glucose, islet function, and insulin sensitivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Although \u223c70% of mice developed severe diabetes after treatment cessation, \u223c30% were essentially cured, maintaining near-normal blood glucose until killed. Another group of NDM mice was initiated on oral glibenclamide (in the drinking water), and the dose was titrated daily, to maintain blood glucose &amp;lt;200 mg\/dL. In this case, \u223c30% were also essentially cured; they were weaned from the drug after \u223c4 weeks and again subsequently maintained near-normal blood glucose. These cured mice maintain normal insulin content and were more sensitive to insulin than control mice, a compensatory mechanism that together with basal insulin secretion may be sufficient to maintain near-normal glucose levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>At least in a subset of animals, early sulfonylurea treatment leads to permanent remission of NDM. These cured animals exhibit insulin-hypersensitivity. Although untreated NDM mice rapidly lose insulin content and progress to permanently extremely elevated blood glucose levels, early tight control of blood glucose may permit this insulin-hypersensitivity, in combination with maintained basal insulin secretion, to provide long-term remission.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db11-0538","type":"journal-article","created":{"date-parts":[[2011,8,4]],"date-time":"2011-08-04T04:09:27Z","timestamp":1312430967000},"page":"2515-2522","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":33,"title":["Acute Sulfonylurea Therapy at Disease Onset Can Cause Permanent Remission of KATP-Induced Diabetes"],"prefix":"10.2337","volume":"60","author":[{"given":"Maria Sara","family":"Remedi","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, and Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia E.","family":"Agapova","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, and Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arpita K.","family":"Vyas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Hruz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin G.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, and Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2011,9,16]]},"reference":[{"key":"2022031222510176900_B1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0896-6273(00)80321-9","article-title":"Association and stoichiometry of K(ATP) channel subunits","volume":"18","author":"Clement","year":"1997","journal-title":"Neuron"},{"key":"2022031222510176900_B2","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1126\/science.270.5239.1166","article-title":"Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor","volume":"270","author":"Inagaki","year":"1995","journal-title":"Science"},{"key":"2022031222510176900_B3","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1085\/jgp.110.6.655","article-title":"Octameric stoichiometry of the KATP channel complex","volume":"110","author":"Shyng","year":"1997","journal-title":"J Gen Physiol"},{"key":"2022031222510176900_B4","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":"2022031222510176900_B5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000109601","article-title":"Overview of neonatal diabetes","volume":"12","author":"Hamilton-Shield","year":"2007","journal-title":"Endocr Dev"},{"key":"2022031222510176900_B6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1750-1172-2-12","article-title":"Neonatal diabetes mellitus: a disease linked to multiple mechanisms","volume":"2","author":"Polak","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"2022031222510176900_B7","first-page":"71","article-title":"The genetic basis of neonatal diabetes mellitus","volume":"4","author":"Sperling","year":"2006","journal-title":"Pediatr Endocrinol Rev"},{"key":"2022031222510176900_B8","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.2337\/diabetes.53.10.2719","article-title":"Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients","volume":"53","author":"Vaxillaire","year":"2004","journal-title":"Diabetes"},{"key":"2022031222510176900_B9","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/humu.20838","article-title":"Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism","volume":"30","author":"Flanagan","year":"2009","journal-title":"Hum Mutat"},{"key":"2022031222510176900_B10","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s001250051247","article-title":"ATP-sensitive K+ channels and insulin secretion: their role in health and disease","volume":"42","author":"Ashcroft","year":"1999","journal-title":"Diabetologia"},{"key":"2022031222510176900_B11","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nature04711","article-title":"KATP channels as molecular sensors of cellular metabolism","volume":"440","author":"Nichols","year":"2006","journal-title":"Nature"},{"key":"2022031222510176900_B12","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00424-009-0756-x","article-title":"K(ATP) channelopathies in the pancreas","volume":"460","author":"Remedi","year":"2010","journal-title":"Pflugers Arch"},{"key":"2022031222510176900_B13","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1093\/hmg\/ddi086","article-title":"Relapsing diabetes can result from moderately activating mutations in KCNJ11","volume":"14","author":"Gloyn","year":"2005","journal-title":"Hum Mol Genet"},{"key":"2022031222510176900_B14","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.2337\/db07-0043","article-title":"Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood","volume":"56","author":"Flanagan","year":"2007","journal-title":"Diabetes"},{"key":"2022031222510176900_B15","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1056\/NEJMoa055068","article-title":"Activating mutations in the ABCC8 gene in neonatal diabetes mellitus","volume":"355","author":"Babenko","year":"2006","journal-title":"N Engl J Med"},{"key":"2022031222510176900_B16","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.2337\/db06-1540","article-title":"New ABCC8 mutations in relapsing neonatal diabetes and clinical features","volume":"56","author":"Vaxillaire","year":"2007","journal-title":"Diabetes"},{"key":"2022031222510176900_B17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1463-1326.2007.00772.x","article-title":"Mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period","volume":"9","author":"Patch","year":"2007","journal-title":"Diabetes Obes Metab"},{"key":"2022031222510176900_B18","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1365-2265.2008.03478.x","article-title":"Mutations in the ABCC8 (SUR1 subunit of the K(ATP) channel) gene are associated with a variable clinical phenotype","volume":"71","author":"Klupa","year":"2009","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2022031222510176900_B19","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.1210\/jc.2005-0096","article-title":"The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus","volume":"90","author":"Yorifuji","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031222510176900_B20","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0092-8674(00)80701-1","article-title":"Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes","volume":"100","author":"Koster","year":"2000","journal-title":"Cell"},{"key":"2022031222510176900_B21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.cmet.2008.12.005","article-title":"Secondary consequences of beta cell inexcitability: identification and prevention in a murine model of K(ATP)-induced neonatal diabetes mellitus","volume":"9","author":"Remedi","year":"2009","journal-title":"Cell Metab"},{"key":"2022031222510176900_B22","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/gene.20137","article-title":"Efficient recombination in pancreatic islets by a tamoxifen-inducible Cre-recombinase","volume":"42","author":"Zhang","year":"2005","journal-title":"Genesis"},{"key":"2022031222510176900_B23","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.2337\/db10-0624","article-title":"Conditional gene targeting in mouse pancreatic \u03b2-cells: analysis of ectopic Cre transgene expression in the brain","volume":"59","author":"Wicksteed","year":"2010","journal-title":"Diabetes"},{"key":"2022031222510176900_B24","doi-asserted-by":"crossref","first-page":"e206","DOI":"10.1371\/journal.pmed.0050206","article-title":"Chronic antidiabetic sulfonylureas in vivo: reversible effects on mouse pancreatic beta-cells","volume":"5","author":"Remedi","year":"2008","journal-title":"PLoS Med"},{"key":"2022031222510176900_B25","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.2337\/diabetes.53.10.2713","article-title":"Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy","volume":"53","author":"Sagen","year":"2004","journal-title":"Diabetes"},{"key":"2022031222510176900_B26","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1056\/NEJMoa061759","article-title":"Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations","volume":"355","author":"Pearson","year":"2006","journal-title":"N Engl J Med"},{"key":"2022031222510176900_B27","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1212\/01.wnl.0000268488.51776.53","article-title":"A novel mutation causing DEND syndrome: a treatable channelopathy of pancreas and brain","volume":"69","author":"Shimomura","year":"2007","journal-title":"Neurology"},{"key":"2022031222510176900_B28","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s12098-009-0222-y","article-title":"Transient neonatal diabetes due to activating mutation in the ABCC8 gene encoding SUR1","volume":"76","author":"Batra","year":"2009","journal-title":"Indian J Pediatr"},{"key":"2022031222510176900_B29","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.clinthera.2009.04.003","article-title":"An oral sulfonylurea in the treatment of transient neonatal diabetes mellitus","volume":"31","author":"Loomba-Albrecht","year":"2009","journal-title":"Clin Ther"},{"key":"2022031222510176900_B30","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1464-5491.2009.02704.x","article-title":"Glibenclamide treatment in relapsed transient neonatal diabetes as a result of a KCNJ11 activating mutation (N48D)","volume":"26","author":"Mart\u00edn-Fr\u00edas","year":"2009","journal-title":"Diabet Med"},{"key":"2022031222510176900_B31","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000109636","article-title":"Diabetes in very young children and mutations in the insulin-secreting cell potassium channel genes: therapeutic consequences","volume":"12","author":"Flechtner","year":"2007","journal-title":"Endocr Dev"},{"key":"2022031222510176900_B32","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.2337\/db06-1746","article-title":"A mutation in the TMD0-L0 region of sulfonylurea receptor-1 (L225P) causes permanent neonatal diabetes mellitus (PNDM)","volume":"56","author":"Masia","year":"2007","journal-title":"Diabetes"},{"key":"2022031222510176900_B33","first-page":"E214","article-title":"Glucose clamp technique: a method for quantifying insulin secretion and resistance","volume":"237","author":"DeFronzo","year":"1979","journal-title":"Am J Physiol"},{"key":"2022031222510176900_B34","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.2337\/diabetes.54.9.2503","article-title":"Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy","volume":"54","author":"Hattersley","year":"2005","journal-title":"Diabetes"},{"key":"2022031222510176900_B35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/humu.20124","article-title":"KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes","volume":"25","author":"Massa","year":"2005","journal-title":"Hum Mutat"},{"key":"2022031222510176900_B36","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1210\/jc.2007-1826","article-title":"The G53D mutation in Kir6.2 (KCNJ11) is associated with neonatal diabetes and motor dysfunction in adulthood that is improved with sulfonylurea therapy","volume":"93","author":"Koster","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031222510176900_B37","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/humu.20292","article-title":"Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism","volume":"27","author":"Gloyn","year":"2006","journal-title":"Hum Mutat"},{"key":"2022031222510176900_B38"},{"key":"2022031222510176900_B39","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1210\/en.2006-0152","article-title":"Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes","volume":"147","author":"Hattersley","year":"2006","journal-title":"Endocrinology"},{"key":"2022031222510176900_B40","first-page":"80","article-title":"Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes","volume":"119","author":"Girard","year":"2009","journal-title":"J Clin Invest"},{"key":"2022031222510176900_B41","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.2337\/diabetes.53.suppl_3.S16","article-title":"Five stages of evolving beta-cell dysfunction during progression to diabetes","volume":"53","author":"Weir","year":"2004","journal-title":"Diabetes"},{"key":"2022031222510176900_B42","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00439-004-1216-5","article-title":"Current status of the E23K Kir6.2 polymorphism: implications for type-2 diabetes","volume":"116","author":"Riedel","year":"2005","journal-title":"Hum Genet"},{"key":"2022031222510176900_B43","doi-asserted-by":"crossref","first-page":"573","DOI":"10.2337\/diabetes.52.2.573","article-title":"The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes","volume":"52","author":"Nielsen","year":"2003","journal-title":"Diabetes"},{"key":"2022031222510176900_B44","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.2337\/db09-0025","article-title":"Kir6.2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance","volume":"58","author":"Villareal","year":"2009","journal-title":"Diabetes"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/60\/10\/2515\/399060\/2515.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/60\/10\/2515\/399060\/2515.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:27:02Z","timestamp":1667406422000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/60\/10\/2515\/33433\/Acute-Sulfonylurea-Therapy-at-Disease-Onset-Can"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,16]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2011,9,16]]},"published-print":{"date-parts":[[2011,10,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db11-0538","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,16]]}}}