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Besides its well-known role for bone mineralization, FGF-23 is discussed as a marker for cardiovascular disease. We investigated whether FGF-23 has any effects on the endocrine pancreas of mice by determining insulin secretion, electrical activity, intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and apoptosis. Acute application of FGF-23 (10 to 500\u00a0ng\/ml, i.e., 0.4 to 20\u00a0nM) does not affect insulin release of murine islets, while prolonged exposure leads to a 21% decrease in glucose-stimulated secretion. The present study shows for the first time that FGF-23 (100 or 500\u00a0ng\/ml) partially protects against impairment of insulin secretion and apoptotic cell death induced by glucolipotoxicity. The reduction of apoptosis by FGF-23 is approximately twofold higher compared to FGF-21 or FGF-15\/19. In contrast to FGF-23 and FGF-21, FGF-15\/19 is clearly pro-apoptotic under control conditions. The beneficial effect of FGF-23 against glucolipotoxicity involves interactions with the stimulus-secretion cascade of beta-cells. Electrical activity and the rise in the cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration of islets in response to acute glucose stimulation increase after glucolipotoxic culture (48\u00a0h). Co-culture with FGF-23 further elevates the glucose-mediated effects on both parameters. Protection against apoptosis and glucolipotoxic impairment of insulin release by FGF-23 is prevented, when calcineurin is inhibited by tacrolimus or when c-Jun N-terminal kinase (JNK) is blocked by SP600125. In conclusion, our data suggest that FGF-23 can activate compensatory mechanisms to maintain beta-cell function and integrity of islets of Langerhans during excessive glucose and lipid supply.\n                  <\/jats:p>","DOI":"10.1007\/s00424-022-02772-x","type":"journal-article","created":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T19:56:30Z","timestamp":1669578990000},"page":"309-322","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["FGF-23 protects cell function and viability in murine pancreatic islets challenged by glucolipotoxicity"],"prefix":"10.1007","volume":"475","author":[{"given":"Betina","family":"Pajaziti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Yosy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga V.","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1572-9235","authenticated-orcid":false,"given":"Martina","family":"D\u00fcfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"2772_CR1","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S2213-8587(18)30051-2","volume":"6","author":"E Ahlqvist","year":"2018","unstructured":"Ahlqvist E, Storm P, K\u00e4r\u00e4j\u00e4m\u00e4ki A et al (2018) Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. 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