{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T14:16:07Z","timestamp":1782828967041,"version":"3.54.5"},"reference-count":44,"publisher":"The Company of Biologists","issue":"11-12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,11,5]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>The events that contribute to the expansion of \u03b2-cell mass and enhanced \u03b2-cell function in insulin-resistant states have not been elucidated fully. Recently, we showed that \u03b2-cell adaptation failed dramatically in adult, insulin-resistant POKO mice, which contrasts with the appropriate expansion of \u03b2 cells in their ob\/ob littermates. Thus, we hypothesised that characterisation of the islets in these mouse models at an early age should provide a unique opportunity to: (1) identify mechanisms involved in sensing insulin resistance at the level of the \u03b2 cells, (2) identify molecular effectors that contribute to increasing \u03b2-cell mass and function, and (3) distinguish primary events from secondary events that are more likely to be present at more advanced stages of diabetes. Our results define the POKO mouse as a model of early lipotoxicity. At 4 weeks of age, it manifests with inappropriate \u03b2-cell function and defects in proliferation markers. Other well-recognised pathogenic effectors that were observed previously in 16-week-old mice, such as increased reactive oxygen species (ROS), macrophage infiltration and endoplasmic reticulum (ER) stress, are also present in both young POKO and young ob\/ob mice, indicating the lack of predictive power with regards to the severity of \u03b2-cell failure. Of interest, the relatively preserved lipidomic profile in islets from young POKO mice contrasted with the large changes in lipid composition and the differences in the chain length of triacylglycerols in the serum, liver, muscle and adipose tissue in adult POKO mice. Later lipotoxic insults in adult \u03b2 cells contribute to the failure of the POKO \u03b2 cell. Our results indicate that the rapid development of insulin resistance and \u03b2-cell failure in POKO mice makes this model a useful tool to study early molecular events leading to insulin resistance and \u03b2-cell failure. Furthermore, comparisons with ob\/ob mice might reveal important adaptive mechanisms in \u03b2 cells with either therapeutic or diagnostic potential.<\/jats:p>","DOI":"10.1242\/dmm.003251","type":"journal-article","created":{"date-parts":[[2009,10,20]],"date-time":"2009-10-20T01:31:51Z","timestamp":1256002311000},"page":"582-592","source":"Crossref","is-referenced-by-count":40,"title":["Adaptation and failure of pancreatic \u03b2 cells in murine models with different degrees of metabolic syndrome"],"prefix":"10.1242","volume":"2","author":[{"given":"Gema","family":"Medina-Gomez","sequence":"first","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke\u2019s Hospital, Cambridge CB2 0QQ, UK"},{"name":"Present address: Departamento de Bioqu\u00edmica, Fisiolog\u00eda y Gen\u00e9tica Molecular, Universidad Rey Juan Carlos, Facultad de Ciencias de la Salud, Avda. de Atenas s\/n, 28922 Alcorc\u00f3n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxman","family":"Yetukuri","sequence":"additional","affiliation":[{"name":"VTT Technical Research Centre of Finland, Tietotie 2, Espoo, P.O. 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