{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:37:51Z","timestamp":1787618271041,"version":"build-2736575974"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/31\/D\/NZ4\/01121"],"award-info":[{"award-number":["2018\/31\/D\/NZ4\/01121"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Histochem Cell Biol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>MOTS-c is a promising regulator of metabolism and energy homeostasis. While its effects have been studied in cell lines, our team aimed to investigate its influence on more complex structures\u2014specifically, isolated pancreatic islets. We used two animal models: the rat, which is commonly studied, and the pig, which shares greater physiological similarities with humans. This study assessed the expression and secretion of insulin and glucagon, the expression of their receptors, cell viability, and cell death following MOTS-c treatment of the islets. Additionally, we examined how MOTS-c secretion is affected by different incubation media, such as the presence of free fatty acids, pancreatic hormones, and different glucose concentrations. The results indicate that MOTS-c impacts pancreatic islet physiology by, for example, reducing insulin and glucagon secretion and enhancing cell viability. Notably, the effects differed between the two species, which may be attributed to anatomical differences in their pancreatic islets or structural variations in rat and pig MOTS-c. These facts may lead to the conclusion that if MOTS-c may be helpful in human medicine, the pig model should be considered another valuable choice.<\/jats:p>","DOI":"10.1007\/s00418-025-02391-4","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:45:15Z","timestamp":1749203115000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MOTS-c modulates pancreatic islet function in rats and pigs in vitro"],"prefix":"10.1007","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5543-7037","authenticated-orcid":false,"given":"Jakub","family":"Bie\u0144","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-6905","authenticated-orcid":false,"given":"Ewa","family":"Pruszynska-Oszmalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-0223","authenticated-orcid":false,"given":"Pawel","family":"Kolodziejski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-7585","authenticated-orcid":false,"given":"Natalia","family":"Leciejewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-5578","authenticated-orcid":false,"given":"Dawid","family":"Szczepankiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8798-991X","authenticated-orcid":false,"given":"Emilia","family":"Grz\u0119da","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9792-1145","authenticated-orcid":false,"given":"Maciej","family":"Sassek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"issue":"11","key":"2391_CR1","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1007\/s00125-005-1956-3","volume":"48","author":"P Arner","year":"2005","unstructured":"Arner P (2005) Resistin: yet another adipokine tells us that men are not mice. Diabetologia 48(11):2203\u20132205. https:\/\/doi.org\/10.1007\/s00125-005-1956-3","journal-title":"Diabetologia"},{"issue":"6","key":"2391_CR2","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s00418-024-02274-0","volume":"161","author":"J Bie\u0144","year":"2024","unstructured":"Bie\u0144 J, Pruszynska E, Kolodziejski P et al (2024) MOTS-c regulates pancreatic alpha and beta cell functions in vitro. Histochem Cell Biol 161(6):449\u2013460. https:\/\/doi.org\/10.1007\/s00418-024-02274-0","journal-title":"Histochem Cell Biol"},{"issue":"6","key":"2391_CR3","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1111\/pedi.12685","volume":"19","author":"C Du","year":"2018","unstructured":"Du C, Zhang C, Wu W et al (2018) Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes 19(6):1058\u20131064. https:\/\/doi.org\/10.1111\/pedi.12685","journal-title":"Pediatr Diabetes"},{"issue":"3","key":"2391_CR4","first-page":"201","volume":"110","author":"AC Ericsson","year":"2013","unstructured":"Ericsson AC, Marcus J, Crim MJ et al (2013) A brief history of animal modeling. Mo Med 110(3):201\u2013205","journal-title":"Mo Med"},{"issue":"11","key":"2391_CR5","doi-asserted-by":"publisher","first-page":"6336","DOI":"10.1073\/pnas.101133498","volume":"98","author":"Y Hashimoto","year":"2001","unstructured":"Hashimoto Y, Niikura T, Tajima H et al (2001) A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer\u2019s disease genes and A\u03b2. Proc Natl Acad Sci U S A 98(11):6336\u20136341. https:\/\/doi.org\/10.1073\/pnas.101133498","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"2391_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110384","volume":"9","author":"DT Hoang","year":"2014","unstructured":"Hoang DT, Matsunari H, Nagaya M et al (2014) A conserved rule for pancreatic islet organization. PLoS ONE 9(10):e110384. https:\/\/doi.org\/10.1371\/journal.pone.0110384","journal-title":"PLoS ONE"},{"issue":"13","key":"2391_CR7","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14171","volume":"7","author":"SJ Kim","year":"2019","unstructured":"Kim SJ, Miller B, Mehta HH et al (2019) The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity. Physiol Rep 7(13):e14171. https:\/\/doi.org\/10.14814\/phy2.14171","journal-title":"Physiol Rep"},{"issue":"4","key":"2391_CR8","doi-asserted-by":"publisher","first-page":"109447","DOI":"10.1016\/j.celrep.2021.109447","volume":"36","author":"BS Kong","year":"2021","unstructured":"Kong BS, Min SH, Lee C et al (2021) Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes. Cell Rep 36(4):109447. https:\/\/doi.org\/10.1016\/j.celrep.2021.109447","journal-title":"Cell Rep"},{"issue":"12","key":"2391_CR9","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.2147\/DMSO.S216791","volume":"24","author":"W Kopp","year":"2019","unstructured":"Kopp W (2019) How western diet and lifestyle drive the pandemic of obesity and civilization diseases. Diabetes Metab Syndr Obes Targets Ther 24(12):2221\u20132236. https:\/\/doi.org\/10.2147\/DMSO.S216791","journal-title":"Diabetes Metab Syndr Obes Targets Ther"},{"issue":"3","key":"2391_CR10","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.cmet.2015.02.009","volume":"21","author":"C Lee","year":"2015","unstructured":"Lee C, Zheng J, Drew BG et al (2015) The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 21(3):443\u2013454. https:\/\/doi.org\/10.1016\/j.cmet.2015.02.009","journal-title":"Cell Metab"},{"issue":"953","key":"2391_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175835","volume":"15","author":"P Lu","year":"2023","unstructured":"Lu P, Li X, Li B et al (2023) The mitochondrial-derived peptide MOTS-c suppresses ferroptosis and alleviates acute lung injury induced by myocardial ischemia reperfusion via PPAR\u03b3 signaling pathway. Eur J Pharmacol 15(953):175835. https:\/\/doi.org\/10.1016\/j.ejphar.2023.175835","journal-title":"Eur J Pharmacol"},{"issue":"621","key":"2391_CR12","doi-asserted-by":"publisher","first-page":"eabd5758","DOI":"10.1126\/scitranslmed.abd5758","volume":"13","author":"JK Lunney","year":"2021","unstructured":"Lunney JK, Van Goor A, Walker KE et al (2021) Importance of the pig as a human biomedical model. Sci Transl Med 13(621):eabd5758. https:\/\/doi.org\/10.1126\/scitranslmed.abd5758","journal-title":"Sci Transl Med"},{"issue":"16","key":"2391_CR13","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.2147\/DMSO.S403934","volume":"12","author":"YH Luo","year":"2023","unstructured":"Luo YH, Xie L, Li JY et al (2023) Serum MOTS-C levels are decreased in obese children and associated with vascular endothelial function. Diabetes Metab Syndr Obes 12(16):1013\u20131020. https:\/\/doi.org\/10.2147\/DMSO.S403934","journal-title":"Diabetes Metab Syndr Obes"},{"issue":"19","key":"2391_CR14","doi-asserted-by":"publisher","first-page":"11991","DOI":"10.3390\/ijms231911991","volume":"23","author":"Z Mohtashami","year":"2022","unstructured":"Mohtashami Z, Singh M, Salimiaghdam N et al (2022) MOTS-c, the most recent mitochondrial derived peptide in human aging and age-related diseases. Int J Mol Sci 23(19):11991. https:\/\/doi.org\/10.3390\/ijms231911991","journal-title":"Int J Mol Sci"},{"issue":"3","key":"2391_CR15","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1083\/jcb.19.3.593","volume":"19","author":"MM Nass","year":"1963","unstructured":"Nass MM, Nass S (1963) Intramitochondrial fibers with DNA characteristics: I. Fixation and electron staining reactions. J Cell Biol 19(3):593\u2013611. https:\/\/doi.org\/10.1083\/jcb.19.3.593","journal-title":"J Cell Biol"},{"issue":"2","key":"2391_CR16","doi-asserted-by":"publisher","first-page":"e12993","DOI":"10.15252\/emmm.202012993","volume":"13","author":"N Ran","year":"2021","unstructured":"Ran N, Lin C, Leng L et al (2021) MOTS-c promotes phosphorodiamidate morpholino oligomer uptake and efficacy in dystrophic mice. EMBO Mol Med 13(2):e12993. https:\/\/doi.org\/10.15252\/emmm.202012993","journal-title":"EMBO Mol Med"},{"key":"2391_CR17","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1101\/sqb.1953.018.01.020","volume":"18","author":"JD Watson","year":"1953","unstructured":"Watson JD, Crick FH (1953) The structure of DNA. Cold Spring Harb Symp Quant Biol 18:123\u2013131. https:\/\/doi.org\/10.1101\/sqb.1953.018.01.020","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"2391_CR18","unstructured":"World Anti-Doping Agency. World anti-doping code international standard prohibited list 2025 [2024 Nov 24]. www.wada-ama.org\/sites\/default\/files\/2024-09\/2025list_en_final_clean_12_september_2024.pdf"},{"issue":"2","key":"2391_CR19","doi-asserted-by":"publisher","first-page":"285","DOI":"10.3724\/abbs.2023006","volume":"55","author":"J Wu","year":"2023","unstructured":"Wu J, Xiao D, Yu K et al (2023) The protective effect of the mitochondrial-derived peptide MOTS-c on LPS-induced septic cardiomyopathy: effect of MOTS-c on septic cardiomyopathy. Acta Biochim Biophys Sin (Shanghai) 55(2):285\u2013294. https:\/\/doi.org\/10.3724\/abbs.2023006","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"2391_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105987","volume":"175","author":"Y Yin","year":"2022","unstructured":"Yin Y, Pan Y, He J et al (2022) The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. Pharmacol Res 175:105987. https:\/\/doi.org\/10.1016\/j.phrs.2021.105987","journal-title":"Pharmacol Res"},{"key":"2391_CR21","doi-asserted-by":"publisher","first-page":"5369","DOI":"10.1111\/jcmm.17551","volume":"26","author":"P Zhong","year":"2022","unstructured":"Zhong P, Peng J, Hu Y et al (2022) Mitochondrial derived peptide MOTS-c prevents the development of heart failure under pressure overload conditions in mice. J Cell Mol Med 26:5369\u20135378. https:\/\/doi.org\/10.1111\/jcmm.17551","journal-title":"J Cell Mol Med"}],"container-title":["Histochemistry and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00418-025-02391-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00418-025-02391-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00418-025-02391-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:26:58Z","timestamp":1768390018000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00418-025-02391-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["2391"],"URL":"https:\/\/doi.org\/10.1007\/s00418-025-02391-4","relation":{},"ISSN":["0948-6143","1432-119X"],"issn-type":[{"value":"0948-6143","type":"print"},{"value":"1432-119X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]},"assertion":[{"value":"14 May 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"64"}}