{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:56:59Z","timestamp":1786114619530,"version":"build-2736575974"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center of Excellence \u201cMetastem\u201d","award":["#312437"],"award-info":[{"award-number":["#312437"]}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF22OC0078484"],"award-info":[{"award-number":["NNF22OC0078484"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>KATP-channel-related hyperinsulinism (KATPHI) is a rare genetic disorder of the pancreatic beta cells, manifesting as life-threatening hypoglycemia in neonates due to excessive insulin secretion. Management of the severe diffuse form of KATPHI currently lacks treatment options, as the first-line therapy octreotide is often insufficiently effective, necessitating radical pancreatectomy in many patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we differentiated stem cells carrying the KATPHI-causing mutation KCNJ11-\/- to stem cell-derived islets (SC-islets) to develop new pharmaceutical therapies for KATPHI. We tested seven candidate molecules in vitro and the most effective ones in vivo in immunocompromised mice that were transplanted with the human KCNJ11-\/- SC-islets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>KCNJ11 -\/- SC-islets inappropriately secreted 3.9 times more insulin in low glucose than KCNJ11+\/+ controls. Transplanted KCNJ11-\/- SC-islets caused persistent hyperinsulinemia and hypoglycemia to the recipient mice. We tested acyl-ghrelin identified in our in vitro experiments and its long-acting analogue relamorelin in these mice. Acyl-ghrelin and relamorelin alone increased fasting blood glucose. Combining relamorelin with octreotide increased blood glucose synergistically, ie, more than the sum of each drug alone, reverting hypoglycemia to normoglycemia while reducing the excessive insulin secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We show that ghrelin-receptor agonists have acute anti-hypoglycemic effects in a humanized mouse model of KATPHI, especially when combined with octreotide. Relamorelin has been tested in &amp;gt;650 diabetic adults with little side effects, leading us to propose relamorelin\u2013octreotide combination for further development as a therapeutic candidate for severe KATPHI patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/stcltm\/szag055","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:21:08Z","timestamp":1779103268000},"source":"Crossref","is-referenced-by-count":0,"title":["Ghrelin and relamorelin counteract hypoglycemia in mice engrafted with congenital hyperinsulinism stem cell-derived islets"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-5548","authenticated-orcid":false,"given":"V\u00e4in\u00f6","family":"Lithovius","sequence":"first","affiliation":[{"name":"Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki , Helsinki, 00290,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam","family":"Montaser","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki , Helsinki, 00290,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonna","family":"Saarim\u00e4ki-Vire","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki , Helsinki, 00290,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki , Helsinki, 00290,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Barsby","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki , Helsinki, 00290,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Balboa","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki , Helsinki, 00290,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Otonkoski","sequence":"additional","affiliation":[{"name":"Stem Cells and Metabolism Research Program of the Faculty of Medicine, University of Helsinki , Helsinki, 00290,","place":["Finland"]},{"name":"Children\u2019s Hospital, Helsinki University Hospital , Helsinki, 00290,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"2026080517164851400_szag055-B1","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.2337\/db08-1084","article-title":"The barrier of hypoglycemia in diabetes","volume":"57","author":"Cryer","year":"2008","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1530\/EJE-12-0673","article-title":"Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism","volume":"168","author":"Kapoor","year":"2013","journal-title":"Eur J Endocrinol."},{"key":"2026080517164851400_szag055-B3","doi-asserted-by":"crossref","first-page":"E355","DOI":"10.1210\/jc.2012-2169","article-title":"Genotype and phenotype correlations in 417 children with congenital hyperinsulinism","volume":"98","author":"Snider","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"key":"2026080517164851400_szag055-B4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s11154-020-09548-7","article-title":"Hyperinsulinemic hypoglycemia in children and adolescents: recent advances in understanding of pathophysiology and management","volume":"21","author":"G\u00fcemes","year":"2020","journal-title":"Rev Endocr Metab Disord"},{"key":"2026080517164851400_szag055-B5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1159\/000531766","article-title":"International guidelines for the diagnosis and management of hyperinsulinism","volume":"97","author":"De Leon","year":"2024","journal-title":"Horm Res Paediatr."},{"key":"2026080517164851400_szag055-B6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jpedsurg.2018.10.030","article-title":"Surgical treatment of congenital hyperinsulinism: results from 500 pancreatectomies in neonates and children","volume":"54","author":"Adzick","year":"2019","journal-title":"J Pediatr Surg."},{"key":"2026080517164851400_szag055-B7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2337\/diabetes.55.01.06.db05-1128","article-title":"Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography","volume":"55","author":"Otonkoski","year":"2006","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B8","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/312446a0","article-title":"Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells","volume":"312","author":"Ashcroft","year":"1984","journal-title":"Nature."},{"key":"2026080517164851400_szag055-B9","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1172\/JCI58400","article-title":"In vitro insulin secretion by pancreatic tissue from infants with diazoxide-resistant congenital hyperinsulinism deviates from model predictions","volume":"121","author":"Henquin","year":"2011","journal-title":"J Clin Invest"},{"key":"2026080517164851400_szag055-B10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1530\/EJE-11-0874","article-title":"Successful treatment of congenital hyperinsulinism with long-acting release octreotide","volume":"166","author":"Le Quan Sang","year":"2012","journal-title":"Eur J Endocrinol."},{"key":"2026080517164851400_szag055-B11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/dmcn.14039","article-title":"The effect of hypoglycaemia on neurocognitive outcome in children and adolescents with transient or persistent congenital hyperinsulinism","volume":"61","author":"Muukkonen","year":"2019","journal-title":"Dev Med Child Neurol."},{"key":"2026080517164851400_szag055-B12","doi-asserted-by":"crossref","first-page":"580642","DOI":"10.3389\/fendo.2020.580642","article-title":"Risk factors for adverse neurodevelopment in transient or persistent congenital hyperinsulinism","volume":"11","author":"Roeper","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026080517164851400_szag055-B13","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.1210\/jc.2015-2539","article-title":"High risk of diabetes and neurobehavioral deficits in individuals with surgically treated hyperinsulinism","volume":"100","author":"Lord","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"key":"2026080517164851400_szag055-B14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1399-5448.2009.00547.x","article-title":"Necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism","volume":"11","author":"Laje","year":"2010","journal-title":"Pediatr Diabetes."},{"key":"2026080517164851400_szag055-B15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/pds.4144","article-title":"Octreotide use and safety in infants with hyperinsulinism","volume":"26","author":"McMahon","year":"2017","journal-title":"Pharmacoepidemiol Drug Saf."},{"key":"2026080517164851400_szag055-B16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1056\/NEJMc2312807","article-title":"Adjuvant alpelisib therapy for congenital hyperinsulinism","volume":"390","author":"Dauleh","year":"2024","journal-title":"N Engl J Med."},{"key":"2026080517164851400_szag055-B17","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1210\/clinem\/dgad648","article-title":"Dasiglucagon for the treatment of congenital hyperinsulinism: a randomized phase 3 trial in infants and children","volume":"109","author":"Thornton","year":"2024","journal-title":"J Clin Endocrinol Metab."},{"key":"2026080517164851400_szag055-B18","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.2337\/db22-1039","article-title":"Optimization of a glucagon-like peptide 1 receptor antagonist antibody for treatment of hyperinsulinism","volume":"72","author":"Peterson","year":"2023","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B19","doi-asserted-by":"crossref","first-page":"10402","DOI":"10.1073\/pnas.95.18.10402","article-title":"Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice","volume":"95","author":"Miki","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026080517164851400_szag055-B20","doi-asserted-by":"crossref","first-page":"37176","DOI":"10.1074\/jbc.M206757200","article-title":"Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose","volume":"277","author":"Shiota","year":"2002","journal-title":"J Biol Chem."},{"key":"2026080517164851400_szag055-B21","doi-asserted-by":"crossref","first-page":"837450","DOI":"10.3389\/fendo.2022.837450","article-title":"Stem cell based models in congenital hyperinsulinism \u2013 perspective on practicalities and possibilities","volume":"13","author":"Lithovius","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026080517164851400_szag055-B22","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.stem.2023.04.002","article-title":"Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes","volume":"30","author":"Hogrebe","year":"2023","journal-title":"Cell Stem Cell."},{"key":"2026080517164851400_szag055-B23","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/s41587-022-01219-z","article-title":"Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells","volume":"40","author":"Balboa","year":"2022","journal-title":"Nat Biotechnol."},{"key":"2026080517164851400_szag055-B24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.stemcr.2018.12.012","article-title":"Acquisition of dynamic function in human stem cell-derived \u03b2 cells","volume":"12","author":"Velazco-Cruz","year":"2019","journal-title":"Stem Cell Reports."},{"key":"2026080517164851400_szag055-B25","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41587-020-0430-6","article-title":"Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells","volume":"38","author":"Hogrebe","year":"2020","journal-title":"Nat Biotechnol."},{"key":"2026080517164851400_szag055-B26","first-page":"49","article-title":"Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes","volume":"1838","author":"Gloyn","year":"2004","journal-title":"N Engl J Med."},{"key":"2026080517164851400_szag055-B27","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1007\/s00125-024-06194-5","article-title":"Non-invasive quantification of stem cell-derived islet graft size and composition","volume":"67","author":"Lithovius","year":"2024","journal-title":"Diabetologia."},{"key":"2026080517164851400_szag055-B28","doi-asserted-by":"crossref","first-page":"101711","DOI":"10.1016\/j.xpro.2022.101711","article-title":"Differentiating functional human islet-like aggregates from pluripotent stem cells","volume":"3","author":"Barsby","year":"2022","journal-title":"STAR Protoc."},{"key":"2026080517164851400_szag055-B29","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1007\/s00125-020-05346-7","article-title":"SUR1-mutant iPS cell-derived islets recapitulate the pathophysiology of congenital hyperinsulinism","volume":"64","author":"Lithovius","year":"2021","journal-title":"Diabetologia."},{"key":"2026080517164851400_szag055-B30","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.2337\/db17-0029","article-title":"Functional and metabolomic consequences of KATP channel inactivation in human islets","volume":"66","author":"Li","year":"2017","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B31","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.2337\/db12-0166","article-title":"GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel","volume":"61","author":"Calabria","year":"2012","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B32","doi-asserted-by":"crossref","first-page":"855","DOI":"10.2337\/diab.15.12.855","article-title":"Interrelationship of glucagon, insulin and glucose. The insulinogenic effect of glucagon","volume":"15","author":"Samols","year":"1966","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B33","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.2337\/db10-0504","article-title":"Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans","volume":"59","author":"Tong","year":"2010","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B34","doi-asserted-by":"crossref","first-page":"110835","DOI":"10.1016\/j.mce.2020.110835","article-title":"Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels","volume":"511","author":"Lindqvist","year":"2020","journal-title":"Mol Cell Endocrinol."},{"key":"2026080517164851400_szag055-B35","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/apt.15711","article-title":"Overall safety of relamorelin in adults with diabetic gastroparesis: analysis of phase 2a and 2b trial data","volume":"51","author":"Camilleri","year":"2020","journal-title":"Aliment Pharmacol Ther."},{"key":"2026080517164851400_szag055-B36","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1053\/j.gastro.2017.07.035","article-title":"Efficacy and safety of relamorelin in diabetics with symptoms of gastroparesis: a randomized, placebo-controlled study","volume":"153","author":"Camilleri","year":"2017","journal-title":"Gastroenterology."},{"key":"2026080517164851400_szag055-B37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1113\/jphysiol.2004.066563","article-title":"GABAB receptor activation inhibits exocytosis in rat pancreatic \u03b2-cells by G-protein-dependent activation of calcineurin: GABAB receptors and pancreatic islet function","volume":"559","author":"Braun","year":"2004","journal-title":"J Physiol."},{"key":"2026080517164851400_szag055-B38","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1038\/s41467-020-15717-8","article-title":"Paracrine control of \u03b1-cell glucagon exocytosis is compromised in human type-2 diabetes","volume":"11","author":"Omar-Hmeadi","year":"2020","journal-title":"Nat Commun."},{"key":"2026080517164851400_szag055-B39","doi-asserted-by":"crossref","first-page":"545638","DOI":"10.3389\/fendo.2020.545638","article-title":"Possible new strategies for the treatment of congenital hyperinsulinism","volume":"11","author":"Sikimic","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026080517164851400_szag055-B40","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00125-017-4447-4","article-title":"GIP(3-30)NH2 is an efficacious GIP receptor antagonist in humans: a randomised, double-blinded, placebo-controlled, crossover study","volume":"61","author":"Gasbjerg","year":"2018","journal-title":"Diabetologia."},{"key":"2026080517164851400_szag055-B41","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cmet.2018.01.015","article-title":"Paracrine interactions within the pancreatic islet determine the glycemic set point","volume":"27","author":"Rodriguez-Diaz","year":"2018","journal-title":"Cell Metab."},{"key":"2026080517164851400_szag055-B42","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.cmet.2015.01.006","article-title":"Suppression of insulin production and secretion by a decretin hormone","volume":"21","author":"Alfa","year":"2015","journal-title":"Cell Metab."},{"key":"2026080517164851400_szag055-B43","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1210\/en.2009-0996","article-title":"Disruption of the dopamine D2 receptor impairs insulin secretion and causes glucose intolerance","volume":"151","author":"Garc\u00eda-Tornad\u00fa","year":"2010","journal-title":"Endocrinology."},{"key":"2026080517164851400_szag055-B44","first-page":"E317","article-title":"5-Hydroxytryptamine-1 receptor activation inhibits endocrine pancreatic secretion in humans","volume":"274","author":"Coulie","year":"1998","journal-title":"Am J Physiol"},{"key":"2026080517164851400_szag055-B45","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/nbt.3033","article-title":"Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells","volume":"32","author":"Rezania","year":"2014","journal-title":"Nat Biotechnol."},{"key":"2026080517164851400_szag055-B46","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.stem.2025.07.006","article-title":"Reconstruction of endocrine subtype-complete human pluripotent stem cell-derived islets with capacity for hypoglycemia protection in vivo","volume":"32","author":"Meng","year":"2025","journal-title":"Cell Stem Cell."},{"key":"2026080517164851400_szag055-B47","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1111\/ajt.17076","article-title":"Elevated islet prohormone ratios as indicators of insulin dependency in auto-islet transplant recipients","volume":"22","author":"Chen","year":"2022","journal-title":"Am J Transplant."},{"key":"2026080517164851400_szag055-B48","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1007\/s00125-024-06163-y","article-title":"RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function","volume":"67","author":"Ibrahim","year":"2024","journal-title":"Diabetologia."},{"key":"2026080517164851400_szag055-B49","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1007\/s00125-025-06474-8","article-title":"Stem-cell-derived beta cells mature metabolically upon murine engraftment","volume":"68","author":"V\u00e4h\u00e4kangas","year":"2025","journal-title":"Diabetologia."},{"key":"2026080517164851400_szag055-B50","doi-asserted-by":"crossref","first-page":"514","DOI":"10.2337\/db24-0119","article-title":"IER3IP1 mutations cause neonatal diabetes due to impaired proinsulin trafficking","volume":"74","author":"Montaser","year":"2025","journal-title":"Diabetes."},{"key":"2026080517164851400_szag055-B51","doi-asserted-by":"crossref","first-page":"eadl4390","DOI":"10.1126\/scitranslmed.adl4390","article-title":"Clinically compliant enrichment of human pluripotent stem cell\u2013derived islets","volume":"17","author":"Rajaei","year":"2025","journal-title":"Sci Transl Med"},{"key":"2026080517164851400_szag055-B52","doi-asserted-by":"crossref","first-page":"e12705","DOI":"10.1111\/jne.12705","article-title":"Ghrelin regulation of glucose metabolism","volume":"31","author":"Gray","year":"2019","journal-title":"J Neuroendocrinol"},{"key":"2026080517164851400_szag055-B53","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.cmet.2016.08.020","article-title":"Single-cell transcriptome profiling of human pancreatic islets in health and type 2 diabetes","volume":"24","author":"Segerstolpe","year":"2016","journal-title":"Cell Metab."},{"key":"2026080517164851400_szag055-B54","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1007\/s00125-016-4033-1","article-title":"Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies Delta cells as a principal target for ghrelin in mouse islets","volume":"59","author":"Adriaenssens","year":"2016","journal-title":"Diabetologia."},{"key":"2026080517164851400_szag055-B55","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.molmet.2016.04.007","article-title":"Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates Delta cells and promotes somatostatin release from pancreatic islets","volume":"5","author":"DiGruccio","year":"2016","journal-title":"Mol Metab."},{"key":"2026080517164851400_szag055-B56","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1056\/NEJM199801223380404","article-title":"Familial hyperinsulinism caused by an activating glucokinase mutation","volume":"338","author":"Glaser","year":"1998","journal-title":"N Engl J Med."},{"key":"2026080517164851400_szag055-B57","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1038\/s41588-022-01204-x","article-title":"Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism","volume":"54","author":"Wakeling","year":"2022","journal-title":"Nat Genet."},{"key":"2026080517164851400_szag055-B58","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature."},{"key":"2026080517164851400_szag055-B59","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0167-0115(02)00067-8","article-title":"The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas","volume":"107","author":"Wierup","year":"2002","journal-title":"Regul Pept."},{"key":"2026080517164851400_szag055-B60","doi-asserted-by":"crossref","first-page":"5083","DOI":"10.1210\/jcem.86.10.8098","article-title":"Ghrelin, a natural GH secratagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans","volume":"86","author":"Broglio","year":"2001","journal-title":"J Clin Endocrinol Metab."},{"key":"2026080517164851400_szag055-B61","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.2337\/db07-0345","article-title":"Ghrelin uses G\u03b1i2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet \u03b2-cells","volume":"56","author":"Dezaki","year":"2007","journal-title":"Diabetes"},{"key":"2026080517164851400_szag055-B62","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2337\/dc12-1128","article-title":"Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying","volume":"36","author":"Shin","year":"2013","journal-title":"Diabetes Care."},{"key":"2026080517164851400_szag055-B63","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/cen.12075","article-title":"Efficacy and safety of long-term, continuous subcutaneous octreotide infusion for patients with different subtypes of KATP-channel hyperinsulinism","volume":"78","author":"Yorifuji","year":"2013","journal-title":"Clin Endocrinol (Oxf)."},{"key":"2026080517164851400_szag055-B64","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1056\/NEJM199601253340408","article-title":"Octreotide","volume":"334","author":"Lamberts","year":"1996","journal-title":"N Engl J Med."},{"key":"2026080517164851400_szag055-B65","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nrgastro.2016.119","article-title":"Necrotizing enterocolitis: new insights into pathogenesis and mechanisms","volume":"13","author":"Ni\u00f1o","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"2026080517164851400_szag055-B66","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s42255-023-00944-2","article-title":"Paracrine signalling by pancreatic \u03b4 cells determines the glycaemic set point in mice","volume":"6","author":"Huang","year":"2024","journal-title":"Nat Metab."},{"key":"2026080517164851400_szag055-B67","doi-asserted-by":"crossref","first-page":"e156549","DOI":"10.1172\/jci.insight.156549","article-title":"Multidimensional analysis and therapeutic development using patient iPSC\u2013derived disease models of wolfram syndrome","volume":"7","author":"Kitamura","year":"2022","journal-title":"JCI Insight."},{"key":"2026080517164851400_szag055-B68","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.stemcr.2018.11.008","article-title":"Single-cell transcriptome profiling of mouse and hESC-derived pancreatic progenitors","volume":"11","author":"Krentz","year":"2018","journal-title":"Stem Cell Reports."},{"key":"2026080517164851400_szag055-B69","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.2337\/db18-0365","article-title":"Pseudotime ordering of single human \u03b2-cells reveals states of insulin production and unfolded protein response","volume":"67","author":"Xin","year":"2018","journal-title":"Diabetes."}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/8\/szag055\/70500220\/szag055.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/8\/szag055\/70500220\/szag055.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T21:16:58Z","timestamp":1785964618000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/doi\/10.1093\/stcltm\/szag055\/8752874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":69,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,7,20]]}},"URL":"https:\/\/doi.org\/10.1093\/stcltm\/szag055","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,7,20]]},"article-number":"szag055"}}