{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:30:49Z","timestamp":1759775449970,"version":"3.37.3"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"National Key R&D Program of China","award":["2017YFD0501102, 2017YFD0501004, 2016YFD0501003"],"award-info":[{"award-number":["2017YFD0501102, 2017YFD0501004, 2016YFD0501003"]}]},{"DOI":"10.13039\/501100003851","name":"Education Department of Heilongjiang Province","doi-asserted-by":"crossref","award":["TSTAU-R2018017"],"award-info":[{"award-number":["TSTAU-R2018017"]}],"id":[{"id":"10.13039\/501100003851","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011787","name":"Science and Technology Department of Heilongjiang Province","doi-asserted-by":"crossref","award":["GX18B018"],"award-info":[{"award-number":["GX18B018"]}],"id":[{"id":"10.13039\/501100011787","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1007\/s00210-020-02023-9","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T20:03:01Z","timestamp":1605902581000},"page":"1031-1043","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fibroblast growth factor 21: a novel long-acting hypoglycemic drug for canine diabetes"],"prefix":"10.1007","volume":"394","author":[{"given":"Xinghao","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoqun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruonan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeboah Kwaku","family":"Opoku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinzhuo","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deshan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-5380","authenticated-orcid":false,"given":"Guiping","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"issue":"7","key":"2023_CR1","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1089\/dia.2015.0364","volume":"18","author":"MB Abraham","year":"2016","unstructured":"Abraham MB, de Bock M, Paramalingam N, O'Grady MJ, Ly TT, George C, Roy A, Spital G, Karula S, Heels K, Gebert R, Fairchild JM, King BR, Ambler GR, Cameron F, Davis EA, Jones TW (2016) Prevention of insulin-induced hypoglycemia in type 1 diabetes with predictive low glucose management system. Diabetes Technol Ther 18(7):436\u2013443. https:\/\/doi.org\/10.1089\/dia.2015.0364","journal-title":"Diabetes Technol Ther"},{"issue":"3","key":"2023_CR2","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.tvjl.2014.09.027","volume":"202","author":"JP Adams","year":"2014","unstructured":"Adams JP, Holder AL, Catchpole B (2014) Recombinant canine single chain insulin analogues: insulin receptor binding capacity and ability to stimulate glucose uptake. Vet J 202(3):436\u2013442. https:\/\/doi.org\/10.1016\/j.tvjl.2014.09.027","journal-title":"Vet J"},{"issue":"10","key":"2023_CR3","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1007\/s00125-005-1921-1","volume":"48","author":"B Catchpole","year":"2005","unstructured":"Catchpole B, Ristic JM, Fleeman LM, Davison LJ (2005) Canine diabetes mellitus: can old dogs teach us new tricks? Diabetologia 48(10):1948\u20131956","journal-title":"Diabetologia"},{"issue":"1","key":"2023_CR4","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/j.1748-5827.2007.00398.x","volume":"49","author":"B Catchpole","year":"2008","unstructured":"Catchpole B, Kennedy LJ, Davison LJ, Ollier WE (2008) Canine diabetes mellitus: from phenotype to genotype. J Small Anim Pract 49(1):4\u201310. https:\/\/doi.org\/10.1111\/j.1748-5827.2007.00398.x","journal-title":"J Small Anim Pract"},{"issue":"2","key":"2023_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.tvjl.2012.11.013","volume":"195","author":"B Catchpole","year":"2013","unstructured":"Catchpole B, Adams JP, Holder AL, Short AD, Ollier WER, Kennedy LJ (2013) Genetics of canine diabetes mellitus: Are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs? Vet J 195(2):139\u2013147","journal-title":"Vet J"},{"issue":"7","key":"2023_CR6","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nrd3180","volume":"9","author":"EC Chao","year":"2010","unstructured":"Chao EC, Henry RR (2010) SGLT2 inhibition\u2014a novel strategy for diabetes treatment. Nat Rev Drug Discov 9(7):551\u2013559","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"2023_CR7","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s00125-003-1074-z","volume":"46","author":"M Cnop","year":"2003","unstructured":"Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, Retzlaff BM, Knopp RH, Brunzell JD, Kahn SE (2003) Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 46(4):459\u2013469. https:\/\/doi.org\/10.1007\/s00125-003-1074-z","journal-title":"Diabetologia"},{"issue":"12","key":"2023_CR8","doi-asserted-by":"publisher","first-page":"6018","DOI":"10.1210\/en.2008-0816","volume":"149","author":"T Coskun","year":"2008","unstructured":"Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, Moller DE, Kharitonenkov A (2008) Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149(12):6018\u20136027","journal-title":"Endocrinology"},{"issue":"1-2","key":"2023_CR9","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.vetimm.2008.06.016","volume":"126","author":"LJ Davison","year":"2008","unstructured":"Davison LJ, Weenink SM, Christie MR, Herrtage ME, Catchpole B (2008) Autoantibodies to GAD65 and IA-2 in canine diabetes mellitus. Vet Immunol Immunopathol 126(1-2):83\u201390","journal-title":"Vet Immunol Immunopathol"},{"issue":"3","key":"2023_CR10","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.cmet.2012.08.002","volume":"16","author":"X Ding","year":"2012","unstructured":"Ding X, Boney-Montoya J, Owen BM, Bookout AL, Coate KC, Mangelsdorf DJ, Kliewer SA (2012) \u03b2Klotho is required for fibroblast growth factor 21 effects on growth and metabolism. Cell Metab 16(3):387\u2013393. https:\/\/doi.org\/10.1016\/j.cmet.2012.08.002","journal-title":"Cell Metab"},{"issue":"Suppl 1 Pt 2","key":"2023_CR11","doi-asserted-by":"publisher","first-page":"26","DOI":"10.2337\/diab.31.1.s26","volume":"31","author":"RL Engerman","year":"1982","unstructured":"Engerman RL, Kramer JW (1982) Dogs with induced or spontaneous diabetes as models for the study of human diabetes mellitus. Diabetes 31(Suppl 1 Pt 2):26\u201329. https:\/\/doi.org\/10.2337\/diab.31.1.s26","journal-title":"Diabetes"},{"issue":"10","key":"2023_CR12","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1210\/me.2010-0142","volume":"24","author":"K Fon Tacer","year":"2010","unstructured":"Fon Tacer K, Bookout AL, Ding X, Kurosu H, John GB, Wang L, Goetz R, Mohammadi M, Kuro-o M, Mangelsdorf DJ, Kliewer SA (2010) Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol 24(10):2050\u20132064. https:\/\/doi.org\/10.1210\/me.2010-0142","journal-title":"Mol Endocrinol"},{"issue":"10","key":"2023_CR13","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1007\/s00125-005-1924-y","volume":"48","author":"EAM Gale","year":"2005","unstructured":"Gale EAM (2005) Do dogs develop autoimmune diabetes? Diabetologia 48(10):1945\u20131947","journal-title":"Diabetologia"},{"issue":"2","key":"2023_CR14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1002\/jcla.20328","volume":"24","author":"MT Goodarzi","year":"2010","unstructured":"Goodarzi MT, Navidi AA, Rezaei M, Babahmadi-Rezaei H (2010) Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes. J Clin Lab Anal 24(2):72\u201376. https:\/\/doi.org\/10.1002\/jcla.20328","journal-title":"J Clin Lab Anal"},{"issue":"1","key":"2023_CR15","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2337\/diacare.24.1.45","volume":"24","author":"SA Grover","year":"2001","unstructured":"Grover SA, Coupal L, Zowall H, Alexander CM, Weiss TW, Gomes DR (2001) How cost-effective is the treatment of dyslipidemia in patients with diabetes but without cardiovascular disease? Diabetes Care 24(1):45\u201350. https:\/\/doi.org\/10.2337\/diacare.24.1.45","journal-title":"Diabetes Care"},{"issue":"1","key":"2023_CR16","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1475-2840-4-5","volume":"4","author":"JS Johansen","year":"2005","unstructured":"Johansen JS, Harris AK, Rychly DJ, Ergul A (2005) Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 4(1):5\u20135","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"2023_CR17","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ab.2012.07.003","volume":"429","author":"A Kanwal","year":"2012","unstructured":"Kanwal A, Singh SP, Grover P, Banerjee SK (2012) Development of a cell-based nonradioactive glucose uptake assay system for SGLT1 and SGLT2. Anal Biochem 429(1):70\u201375","journal-title":"Anal Biochem"},{"issue":"6","key":"2023_CR18","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1172\/jci23606","volume":"115","author":"A Kharitonenkov","year":"2005","unstructured":"Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB (2005) FGF-21 as a novel metabolic regulator. J Clin Invest 115(6):1627\u20131635. https:\/\/doi.org\/10.1172\/jci23606","journal-title":"J Clin Invest"},{"issue":"2","key":"2023_CR19","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1210\/en.2006-1168","volume":"148","author":"A Kharitonenkov","year":"2007","unstructured":"Kharitonenkov A, Wroblewski VJ, Koester A, Chen YF, Clutinger CK, Tigno XT, Hansen BC, Shanafelt AB, Etgen GJ (2007) The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 148(2):774\u2013781. https:\/\/doi.org\/10.1210\/en.2006-1168","journal-title":"Endocrinology"},{"issue":"1-3","key":"2023_CR20","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.ejphar.2012.11.065","volume":"702","author":"LJ Kong","year":"2013","unstructured":"Kong LJ, Feng W, Wright M, Chen Y, Dallas-Yang Q, Zhou YP, Berger JP (2013) FGF21 suppresses hepatic glucose production through the activation of atypical protein kinase C\u03b9\/\u03bb. Eur J Pharmacol 702(1-3):302\u2013308","journal-title":"Eur J Pharmacol"},{"issue":"11","key":"2023_CR21","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.molmed.2004.09.003","volume":"10","author":"H Motohashi","year":"2004","unstructured":"Motohashi H, Yamamoto M (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10(11):549\u2013557","journal-title":"Trends Mol Med"},{"issue":"1","key":"2023_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/jcp.20847","volume":"210","author":"JS Moyers","year":"2007","unstructured":"Moyers JS, Shiyanova TL, Mehrbod F, Dunbar JD, Noblitt TW, Otto KA, Reifel-Miller A, Kharitonenkov A (2007) Molecular determinants of FGF-21 activity-synergy and cross-talk with PPARgamma signaling. J Cell Physiol 210(1):1\u20136. https:\/\/doi.org\/10.1002\/jcp.20847","journal-title":"J Cell Physiol"},{"issue":"1","key":"2023_CR23","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/s0167-4781(00)00067-1","volume":"1492","author":"T Nishimura","year":"2000","unstructured":"Nishimura T, Nakatake Y, Konishi M, Itoh N (2000) Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta 1492(1):203\u2013206. https:\/\/doi.org\/10.1016\/s0167-4781(00)00067-1","journal-title":"Biochim Biophys Acta"},{"issue":"8 Suppl","key":"2023_CR24","doi-asserted-by":"publisher","first-page":"2072S","DOI":"10.1093\/jn\/134.8.2072S","volume":"134","author":"JS Rand","year":"2004","unstructured":"Rand JS (2004) Canine and feline diabetes mellitus: Nature or nurture? J Nutr 134(8 Suppl):2072S\u20132080S","journal-title":"J Nutr"},{"issue":"2","key":"2023_CR25","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.freeradbiomed.2005.04.030","volume":"41","author":"RP Robertson","year":"2006","unstructured":"Robertson RP, Harmon JS (2006) Diabetes, glucose toxicity, and oxidative stress: a case of double jeopardy for the pancreatic islet \u03b2 cell. Free Radic Biol Med 41(2):177\u2013184","journal-title":"Free Radic Biol Med"},{"issue":"6","key":"2023_CR26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129809","volume":"10","author":"EJ Shields","year":"2015","unstructured":"Shields EJ, Lam CJ, Cox AR, Rankin MM, Van Winkle TJ, Hess RS, Kushner JA (2015) Extreme beta-cell deficiency in pancreata of dogs with canine diabetes. PLoS One 10(6):e0129809. https:\/\/doi.org\/10.1371\/journal.pone.0129809","journal-title":"PLoS One"},{"issue":"5","key":"2023_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155598","volume":"11","author":"P Xu","year":"2016","unstructured":"Xu P, Zhang Y, Jiang X, Li J, Song L, Hasson KM, Liu Y, Wu Q, Ren G, Li D (2016) Canine fibroblast growth factor 21 ameliorates hyperglycemia associated with inhibiting hepatic gluconeogenesis and improving pancreatic beta-cell survival in diabetic mice and dogs. PLoS One 11(5):e0155598","journal-title":"PLoS One"},{"issue":"1","key":"2023_CR28","first-page":"15","volume":"14","author":"BA Young","year":"2008","unstructured":"Young BA, Lin E, Korff MV, Simon G, Katon WJ (2008) Diabetes complications severity index and risk of mortality, hospitalization, and healthcare utilization. Am J Manag Care 14(1):15\u201323","journal-title":"Am J Manag Care"},{"issue":"5","key":"2023_CR29","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1007\/s00125-012-2479-3","volume":"55","author":"D Zechner","year":"2012","unstructured":"Zechner D, Spitzner M, Bobrowski A, Knapp N, Kuhla A, Vollmar B (2012) Diabetes aggravates acute pancreatitis and inhibits pancreas regeneration in mice. Diabetologia 55(5):1526\u20131534","journal-title":"Diabetologia"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-020-02023-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-020-02023-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-020-02023-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:09:00Z","timestamp":1620346140000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-020-02023-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,20]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["2023"],"URL":"https:\/\/doi.org\/10.1007\/s00210-020-02023-9","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"type":"print","value":"0028-1298"},{"type":"electronic","value":"1432-1912"}],"subject":[],"published":{"date-parts":[[2020,11,20]]},"assertion":[{"value":"14 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The protocols for all the animal experiments were approved by the Animal Care and Use Committee of the Institute of Materia Medica, China.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}}]}}