{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:04:45Z","timestamp":1790078685926,"version":"4.0.1"},"reference-count":71,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["184767"],"award-info":[{"award-number":["184767"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["219229"],"award-info":[{"award-number":["219229"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["214870"],"award-info":[{"award-number":["214870"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007028","name":"Leona M. & Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["2405-06952"],"award-info":[{"award-number":["2405-06952"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DiaGen Association"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Insulin deficiency (ID) causes severe metabolic defects and death if untreated, while insulin therapy does not fully restore metabolic homeostasis. Leptin therapy corrects metabolic abnormalities and promotes survival in rodents unable to produce insulin, suggesting the existence of insulin-independent glucoregulatory mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize hepatic translational remodeling in severe insulin deficiency and determine whether leptin-responsive translational changes can reveal novel glucoregulatory factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used mice with diphtheria toxin-induced pancreatic \u03b2-cell ablation, resulting in severe ID. We assessed hepatic translation by polysome profiling, ribosome profiling (Ribo-seq), and RNA sequencing. To identify leptin-responsive hepatic factors, we compared the hepatic translatome during intracerebroventricular leptin treatment and following leptin withdrawal. Regenerating islet-derived protein 3 alpha (Reg3\u03b1) was subsequently overexpressed in the liver of ID mice to assess its metabolic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ID suppresses hepatic mechanistic target of rapamycin complex 1 (mTORC1) signaling and global protein synthesis while extensively remodeling the hepatic translatome. Translation of anabolic and glucose-metabolism pathways is reduced, whereas transcripts involved in lipid metabolism are selectively enhanced. Leptin treatment markedly increases hepatic Reg3\u03b1 translation. Hepatic Reg3\u03b1 overexpression significantly improves hyperglycemia in ID mice without altering insulin-stimulated AKT phosphorylation in key metabolic tissues. These findings identify hepatic translational rewiring as an important feature of ID and Reg3\u03b1 as an insulin-independent glucoregulatory factor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/endocr\/bqag100","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T19:21:48Z","timestamp":1788204108000},"source":"Crossref","is-referenced-by-count":0,"title":["Hepatic translational rewiring in insulin deficiency identifies Reg3\u03b1 as an insulin-independent glucoregulatory factor"],"prefix":"10.1210","volume":"167","author":[{"given":"Pryscila","family":"D. S. Teixeira","sequence":"first","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]},{"name":"Diabetes Center of the Faculty of Medicine, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1053-3982","authenticated-orcid":false,"given":"Sarah Mathilda","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]},{"name":"Diabetes Center of the Faculty of Medicine, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3115-2501","authenticated-orcid":false,"given":"Romane","family":"Meurs","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, G\u00e9nopode, University of Lausanne , Lausanne 1015 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2703-4417","authenticated-orcid":false,"given":"Gloria","family":"Ursino","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]},{"name":"Diabetes Center of the Faculty of Medicine, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs","family":"Zahoran","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]},{"name":"Diabetes Center of the Faculty of Medicine, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5543-1719","authenticated-orcid":false,"given":"Giulia","family":"Lucibello","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]},{"name":"Diabetes Center of the Faculty of Medicine, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5479-2096","authenticated-orcid":false,"given":"Marcella","family":"M. Authiat","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4917-2340","authenticated-orcid":false,"given":"Anne-Claude","family":"Gavin","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0194-3257","authenticated-orcid":false,"given":"Giorgio","family":"Ramadori","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]},{"name":"Diabetes Center of the Faculty of Medicine, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-6948","authenticated-orcid":false,"given":"Roberto","family":"Coppari","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism, University of Geneva , Geneva 1211 ,","place":["Switzerland"]},{"name":"Diabetes Center of the Faculty of Medicine, University of Geneva , Geneva 1211 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"6","key":"2026092207121150200_bqag100-B1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/jdi.12094","article-title":"Glucose-stimulated insulin secretion: a newer perspective","volume":"4","author":"Komatsu","year":"2013","journal-title":"J Diabetes Investig"},{"issue":"1-2","key":"2026092207121150200_bqag100-B2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.mce.2011.07.016","article-title":"Mitochondrial signals drive insulin secretion in the pancreatic \u03b2-cell","volume":"353","author":"Wiederkehr","year":"2012","journal-title":"Mol Cell Endocrinol"},{"issue":"6","key":"2026092207121150200_bqag100-B3","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.cell.2012.07.029","article-title":"Pancreatic \u03b2 cell dedifferentiation as a mechanism of diabetic \u03b2 cell failure","volume":"150","author":"Talchai","year":"2012","journal-title":"Cell"},{"issue":"11","key":"2026092207121150200_bqag100-B4","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/ncpendmet0647","article-title":"The replication of beta cells in normal physiology, in disease and for therapy","volume":"3","author":"Butler","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab"},{"issue":"9","key":"2026092207121150200_bqag100-B5","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nrd3757","article-title":"Leptin revisited: its mechanism of action and potential for treating diabetes","volume":"11","author":"Coppari","year":"2012","journal-title":"Nat Rev Drug Discov"},{"issue":"Suppl 1","key":"2026092207121150200_bqag100-B6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/dom.12723","article-title":"When \u03b2-cells fail: lessons from dedifferentiation","volume":"18","author":"Accili","year":"2016","journal-title":"Diabetes Obes Metab"},{"issue":"5","key":"2026092207121150200_bqag100-B7","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.cmet.2010.04.009","article-title":"The stunned beta cell: a brief history","volume":"11","author":"Ferrannini","year":"2010","journal-title":"Cell Metab"},{"key":"2026092207121150200_bqag100-B8","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2025.112277","article-title":"Global type 1 diabetes prevalence, incidence, and mortality estimates 2025: results from the International diabetes Federation Atlas, 11th Edition, and the T1D Index Version 3.0","volume":"225","author":"Ogle","year":"2025","journal-title":"Diabetes Res Clin Pract"},{"issue":"3","key":"2026092207121150200_bqag100-B9","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s00125-018-4763-3","article-title":"Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study","volume":"62","author":"Patterson","year":"2019","journal-title":"Diabetologia"},{"issue":"12","key":"2026092207121150200_bqag100-B10","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1007\/s00125-021-05568-3","article-title":"The management of type 1 diabetes in adults. 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