{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:45:32Z","timestamp":1792788332214,"version":"4.5.0"},"reference-count":40,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Olle Engkvists Stiftelse","id":[{"id":"https:\/\/ror.org\/00r9xw041","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Royal Physiographic Society of Lund","id":[{"id":"https:\/\/ror.org\/05rnj0j91","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Inga and John Hain Foundation"},{"name":"Bertil and Ebon Norlins Foundation"},{"name":"Parkinsonfonden"},{"name":"Anna-Lisa Rosenberg Foundation","id":[{"id":"https:\/\/ror.org\/04qfp7s87","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Parkinson Research Foundation","id":[{"id":"https:\/\/ror.org\/00j7nqv87","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Lund University","id":[{"id":"https:\/\/ror.org\/012a77v79","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>High-fat diet (HFD) combined with streptozotocin (STZ) is widely used to model type 2 diabetes (T2D) in rodents, but is often associated with high mortality, non-responders and inconsistent outcomes. STZ is conventionally administered using body weight-adjusted dosing (mg\/kg), despite evidence that heavier animals, including HFD-fed mice, exhibit more severe glycaemic responses. Here, we performed metabolic phenotyping in chow- and HFD-fed C57BL\/6J mice treated with low or high fixed doses (mg instead of mg\/kg) of anomer-equilibrated STZ. HFD combined with low-dose STZ induced a stable T2D-like phenotype characterized by sustained obesity, moderate hyperglycaemia, insulin resistance and partial \u03b2-cell loss, with low inter-individual variability. In contrast, high-dose STZ induced a type 1 diabetes-like phenotype, with extensive \u03b2-cell loss. A semi-mechanistic mathematical model was developed and validated against independent experimental data, reproducing the observed dynamics of fasting glucose in response to fixed-dose STZ. The model further predicted that weight-adjusted (mg\/kg) dosing could introduce variability in glycaemic responses, particularly in HFD-fed mice. Together, these results demonstrate that fixed-dose, anomer-equilibrated STZ induces a stable T2D-like phenotype, providing an alternative to conventional weight-adjusted dosing in HFD-fed mice.<\/jats:p>","DOI":"10.1242\/dmm.053071","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T06:45:03Z","timestamp":1785998703000},"source":"Crossref","is-referenced-by-count":0,"title":["Fixed-dose streptozotocin combined with high-fat diet induces a stable type 2 diabetes-like phenotype in C57BL\/6J mice"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2581-8832","authenticated-orcid":false,"given":"Claes","family":"Fryklund","sequence":"first","affiliation":[{"name":"Lund University Department of Experimental Medical Science , , 22100 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3805-1674","authenticated-orcid":false,"given":"Christian","family":"Simonsson","sequence":"additional","affiliation":[{"name":"Lund University Department of Experimental Medical Science , , 22100 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Hellberg","sequence":"additional","affiliation":[{"name":"Lund University Department of Experimental Medical Science , , 22100 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2003-5639","authenticated-orcid":false,"given":"Josefin","family":"Malmberg","sequence":"additional","affiliation":[{"name":"Lund University Department of Experimental Medical Science , , 22100 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0739-1150","authenticated-orcid":false,"given":"Karin G.","family":"Stenkula","sequence":"additional","affiliation":[{"name":"Lund University Department of Experimental Medical Science , , 22100 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1829-1008","authenticated-orcid":false,"given":"Maria","family":"Swanberg","sequence":"additional","affiliation":[{"name":"Lund University Department of Experimental Medical Science , , 22100 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"2026091706374874900_DMM053071C1","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. 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