{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:20:54Z","timestamp":1775841654251,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T00:00:00Z","timestamp":1734220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council","award":["App1149976"],"award-info":[{"award-number":["App1149976"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 1 diabetes (T1D) is caused by the immune-mediated loss of pancreatic \u03b2-cells. Hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) is a transcription factor which is crucial for cellular responses to low oxygen. Here, we investigate the role of \u03b2-cell HIF-1\u03b1 in \u03b2-cell death and diabetes after exposure to multiple low-dose streptozotocin (MLDS). MDLS triggers auto-immunity in susceptible animal models, such as non-obese diabetic (NOD) mice. These experiments used a novel mouse model with \u03b2-cell-specific deletion of HIF-1\u03b1 on a NOD background (BIN mice). Mice were given 20 mg\/kg MLDS for 5 consecutive days. Following MLDS, 100% of BIN mice developed frank diabetes versus 33% of floxed-control (FC) littermates and 17% of NOD controls (p &lt; 0.001). BIN mice had obvious loss of \u03b2-cell mass (p &lt; 0.0001) and increased necrotic areas within islets (p &lt; 0.001). To confirm that diabetes was T1D, adoptive transfers of splenocytes from diabetic BIN and FC mice were performed on NOD-SCID (Severe Combined ImmunoDeficiency) recipients. All mice receiving BIN-splenocytes developed frank diabetes, confirming that MLDS induced true T1D. Interestingly, diabetes developed significantly faster in BIN-adoptive transfer mice compared to mice which developed diabetes after receiving an FC-adoptive transfer. These studies demonstrate the importance of \u03b2-cell HIF-1\u03b1 in the preservation of \u03b2-cell mass and avoidance of auto-immunity.<\/jats:p>","DOI":"10.3390\/ijms252413451","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T04:14:52Z","timestamp":1734322492000},"page":"13451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u03b2-Cell Deletion of Hypoxia-Inducible Factor 1\u03b1 (HIF-1\u03b1) Increases Pancreatic \u03b2-Cell Susceptibility to Streptozotocin"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-5257","authenticated-orcid":false,"given":"Josephine","family":"Yu","sequence":"first","affiliation":[{"name":"Centre for Diabetes, Obesity and Endocrinology (CDOE), The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Lalwani","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Obesity and Endocrinology (CDOE), The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2145, Australia"},{"name":"Diabetes and Transcription Factors Group, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8127-9773","authenticated-orcid":false,"given":"Jenny E.","family":"Gunton","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Obesity and Endocrinology (CDOE), The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW 2145, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2145, Australia"},{"name":"Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, November 28). 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