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This study aimed to elucidate how neonatal pancreatic \u03b2-cells become glucose-responsive, using an in vitro protocol involving culture of neonatal islets at low glucose to emulate systemic hypoglycemia. Low-glucose exposure markedly improved glucose responsiveness of neonatal islets by selectively lowering insulin secretion at low glucose concentrations. Unlike adult \u03b2-cells, neonatal \u03b2-cells were depolarized and generated spontaneous action potentials at low glucose, resulting in elevated [Ca2+]i and a blunted response to high glucose. These changes were reversed by brief (1-2\u2005hours) low-glucose culture, which was accompanied by increased KATP channel surface expression and activity. The effects of low-glucose incubation were mimicked by the AMPK agonist AICAR. These insights may inform strategies to restore glucose-regulated insulin secretion in type 2 diabetes.<\/jats:p>","DOI":"10.1210\/endocr\/bqag085","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:57:05Z","timestamp":1785412625000},"source":"Crossref","is-referenced-by-count":1,"title":["Hypoglycemic conditions enhance neonatal \u03b2-cell glucose responsiveness via AMPK\/mTOR-increased KATP channel density"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6034-0856","authenticated-orcid":false,"given":"Ekaterina","family":"Novichkova","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences, Weizmann Institute of Science , Rehovot 7610001 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1551-4114","authenticated-orcid":false,"given":"Haiqiang","family":"Dou","sequence":"additional","affiliation":[{"name":"Institute of 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and Physiology, Department of Physiology, Metabolic Research Unit, Sahlgrenska Academy, Box 432, University of Gothenburg , 405 30 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4649-2093","authenticated-orcid":false,"given":"Caroline","family":"Miranda","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Physiology, Metabolic Research Unit, Sahlgrenska Academy, Box 432, University of Gothenburg , 405 30 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7578-0767","authenticated-orcid":false,"given":"Patrik","family":"Rorsman","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Department of Physiology, Metabolic Research Unit, Sahlgrenska Academy, Box 432, University of Gothenburg , 405 30 Gothenburg ,","place":["Sweden"]},{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford , Oxford OX3 7LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-154X","authenticated-orcid":false,"given":"Aharon","family":"Helman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Food Science and Nutrition, The Robert H Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem , Rehovot 7610001 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7317-629X","authenticated-orcid":false,"given":"Michael D","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, Weizmann Institute of Science , Rehovot 7610001 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