{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:48:12Z","timestamp":1788299292744,"version":"build-2803163510"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Fondi 5x mille"],"award-info":[{"award-number":["Fondi 5x mille"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"DOI":"10.1007\/s40618-022-01812-8","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T17:04:36Z","timestamp":1652893476000},"page":"1741-1748","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Circulating levels of PIN1 and glucose metabolism in young people with obesity"],"prefix":"10.1007","volume":"45","author":[{"given":"M.","family":"Bianchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-975X","authenticated-orcid":false,"given":"M.","family":"Manco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"issue":"5","key":"1812_CR1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1159\/000464144","volume":"87","author":"C Brufani","year":"2017","unstructured":"Brufani C, Tura A, Bedogni G, Luciano R, Sbrignadello S, Fintini D, Cappa M, Weiss R, Manco M (2017) Inside out the ragbag of glucose intolerance in obese adolescents. Horm Res Paediatr 87(5):287\u2013294. https:\/\/doi.org\/10.1159\/000464144","journal-title":"Horm Res Paediatr"},{"issue":"20","key":"1812_CR2","doi-asserted-by":"publisher","first-page":"5064","DOI":"10.3390\/ijms20205064","volume":"20","author":"M Bianchi","year":"2019","unstructured":"Bianchi M, D\u2019Oria V, Braghini MR, Petrini S, Manco M (2019) Liraglutide treatment ameliorates neurotoxicity induced by stable silencing of Pin1. Int J Mol Sci 20(20):5064. https:\/\/doi.org\/10.3390\/ijms20205064","journal-title":"Int J Mol Sci"},{"issue":"8","key":"1812_CR3","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.3390\/ijms19082319","volume":"19","author":"M Bianchi","year":"2018","unstructured":"Bianchi M, Manco M (2018) Pin1 modulation in physiological status and neurodegeneration. Any contribution to the pathogenesis of type 3 diabetes? Int J Mol Sci 19(8):2319. https:\/\/doi.org\/10.3390\/ijms19082319","journal-title":"Int J Mol Sci"},{"issue":"11","key":"1812_CR4","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/nrm2261","volume":"8","author":"KP Lu","year":"2007","unstructured":"Lu KP, Zhou XZ (2007) The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease. Nat Rev Mol Cell Biol 8(11):904\u2013916. https:\/\/doi.org\/10.1038\/nrm2261","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"9","key":"1812_CR5","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.3390\/ijms17091495","volume":"17","author":"Y Nakatsu","year":"2016","unstructured":"Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue Y, Mori K, Sakoda H, Fujishiro M, Ono H, Kushiyama A, Asano T (2016) Physiological and pathogenic roles of prolyl isomerase Pin1 in metabolic regulations via multiple signal transduction pathway modulations. Int J Mol Sci 17(9):1495. https:\/\/doi.org\/10.3390\/ijms17091495","journal-title":"Int J Mol Sci"},{"issue":"23","key":"1812_CR6","doi-asserted-by":"publisher","first-page":"20812","DOI":"10.1074\/jbc.M110.206904","volume":"286","author":"Y Nakatsu","year":"2011","unstructured":"Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi S, Kurihara H, Uchida T, Asano T (2011) Peptidyl-prolyl cis\/trans isomerase NIMA-interacting 1 associates with insulin receptor substrate-1 and enhances insulin actions and adipogenesis. J Boil Chem 286(23):20812\u201322. https:\/\/doi.org\/10.1074\/jbc.M110.206904","journal-title":"J Boil Chem"},{"issue":"10","key":"1812_CR7","doi-asserted-by":"publisher","first-page":"6969","DOI":"10.1074\/jbc.C111.298596","volume":"287","author":"SL Ma","year":"2012","unstructured":"Ma SL, Pastorino L, Zhou XZ, Lu KP (2012) Prolyl isomerase Pin1 promotes amyloid precursor protein (APP) turnover by inhibiting glycogen synthase kinase-3beta (GSK3beta) activity: novel mechanism for Pin1 to protect against Alzheimer disease. J Biol Chem 287(10):6969\u20136973. https:\/\/doi.org\/10.1074\/jbc.C111.298596","journal-title":"J Biol Chem"},{"issue":"1","key":"1812_CR8","first-page":"19","volume":"2","author":"Y Liao","year":"2010","unstructured":"Liao Y, Hung MC (2010) Physiological regulation of Akt activity and stability. Am J Transl Res 2(1):19\u201342","journal-title":"Am J Transl Res"},{"issue":"9","key":"1812_CR9","doi-asserted-by":"publisher","first-page":"4307","DOI":"10.1210\/jcem.86.9.7872","volume":"86","author":"SE Nikoulina","year":"2001","unstructured":"Nikoulina SE, Ciaraldi TP, Carter L, Mudaliar S, Park KS, Henry RR (2001) Impaired muscle glycogen synthase in type 2 diabetes is associated with diminished phosphatidylinositol 3-kinase activation. J Clin Endocrinol Metab 86(9):4307\u20134314. https:\/\/doi.org\/10.1210\/jcem.86.9.7872","journal-title":"J Clin Endocrinol Metab"},{"issue":"28","key":"1812_CR10","doi-asserted-by":"publisher","first-page":"11886","DOI":"10.1074\/jbc.M117.780726","volume":"292","author":"Y Nakatsu","year":"2017","unstructured":"Nakatsu Y, Mori K, Matsunaga Y, Yamamotoya T, Ueda K, Inoue Y, Mitsuzaki-Miyoshi K, Sakoda H, Fujishiro M, Yamaguchi S, Kushiyama A, Ono H, Ishihara H, Asano T (2017) The prolyl isomerase Pin1 increases beta-cell proliferation and enhances insulin secretion. J Biol Chem 292(28):11886\u201311895. https:\/\/doi.org\/10.1074\/jbc.M117.780726","journal-title":"J Biol Chem"},{"issue":"13","key":"1812_CR11","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1093\/eurheartj\/ehu179","volume":"36","author":"F Paneni","year":"2015","unstructured":"Paneni F, Costantino S, Castello L, Battista R, Capretti G, Chiandotto S, D\u2019Amario D, Scavone G, Villano A, Rustighi A, Crea F, Pitocco D, Lanza G, Volpe M, Del Sal G, Luscher TF, Cosentino F (2015) Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes. Eur Heart J 36(13):817\u2013828. https:\/\/doi.org\/10.1093\/eurheartj\/ehu179","journal-title":"Eur Heart J"},{"issue":"92","key":"1812_CR12","first-page":"93","volume":"17","author":"JA Driver","year":"2014","unstructured":"Driver JA, Zhou XZ, Lu KP (2014) Regulation of protein conformation by Pin1 offers novel disease mechanisms and therapeutic approaches in Alzheimer\u2019s disease. Discov Med 17(92):93\u201399","journal-title":"Discov Med"},{"issue":"7083","key":"1812_CR13","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nature04543","volume":"440","author":"L Pastorino","year":"2006","unstructured":"Pastorino L, Sun A, Lu PJ, Zhou XZ, Balastik M, Finn G, Wulf G, Lim J, Li SH, Li X, Xia W, Nicholson LK, Lu KP (2006) The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 440(7083):528\u201334. https:\/\/doi.org\/10.1038\/nature04543","journal-title":"Nature"},{"issue":"6","key":"1812_CR14","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1542\/peds.2014-2391","volume":"135","author":"R Luciano","year":"2015","unstructured":"Luciano R, Barraco GM, Muraca M, Ottino S, Spreghini MR, Sforza RW, Rustico C, Morino GS, Manco M (2015) Biomarkers of Alzheimer disease, insulin resistance, and obesity in childhood. Pediatrics 135(6):1074\u201381. https:\/\/doi.org\/10.1542\/peds.2014-2391","journal-title":"Pediatrics"},{"issue":"5","key":"1812_CR15","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1093\/hmg\/ddab287","volume":"31","author":"Z Balkhiyarova","year":"2022","unstructured":"Balkhiyarova Z, Luciano R, Kaakinen M, Ulrich A, Shmeliov A, Bianchi M, Chioma L, Dallapiccola B, Prokopenko I, Manco M (2022) Relationship between glucose homeostasis and obesity in early life-a study of Italian children and adolescents. Hum Mol Genet 31(5):816\u2013826. https:\/\/doi.org\/10.1093\/hmg\/ddab287","journal-title":"Hum Mol Genet"},{"issue":"2","key":"1812_CR16","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s00592-015-0782-4","volume":"53","author":"B Shashaj","year":"2016","unstructured":"Shashaj B, Luciano R, Contoli B, Morino GS, Spreghini MR, Rustico C, Sforza RW, Dallapiccola B, Manco M (2016) Reference ranges of HOMA-IR in normal-weight and obese young Caucasians. Acta Diabetol 53(2):251\u201360. https:\/\/doi.org\/10.1007\/s00592-015-0782-4","journal-title":"Acta Diabetol"},{"issue":"5","key":"1812_CR17","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/j.jhep.2019.06.031","volume":"71","author":"C Rosso","year":"2019","unstructured":"Rosso C, Kazankov K, Younes R, Esmaili S, Marietti M, Sacco M, Carli F, Gaggini M, Salomone F, M\u00f8ller HJ, Abate ML, Vilstrup H, Gastaldelli A, George J, Gr\u00f8nb\u00e6k H, Bugianesi E (2019) Crosstalk between adipose tissue insulin resistance and liver macrophages in non-alcoholic fatty liver disease. J Hepatol 71(5):1012\u20131021","journal-title":"J Hepatol"},{"issue":"4","key":"1812_CR18","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cmet.2007.08.013","volume":"6","author":"K MacAulay","year":"2007","unstructured":"MacAulay K, Doble BW, Patel S, Hansotia T, Sinclair EM, Drucker DJ, Nagy A, Woodgett JR (2007) Glycogen synthase kinase 3alpha-specific regulation of murine hepatic glycogen metabolism. Cell Metab 6(4):329\u201337. https:\/\/doi.org\/10.1016\/j.cmet.2007.08.013","journal-title":"Cell Metab"},{"issue":"28","key":"1812_CR19","doi-asserted-by":"publisher","first-page":"20692","DOI":"10.1074\/jbc.M113.485730","volume":"288","author":"J Zhang","year":"2013","unstructured":"Zhang J, Nakatsu Y, Shinjo T, Guo Y, Sakoda H, Yamamotoya T, Otani Y, Okubo H, Kushiyama A, Fujishiro M, Fukushima T, Tsuchiya Y, Kamata H, Iwashita M, Nishimura F, Katagiri H, Takahashi S, Kurihara H, Uchida T, Asano T (2013) Par14 protein associates with insulin receptor substrate 1 (IRS-1), thereby enhancing insulin-induced IRS-1 phosphorylation and metabolic actions. J Biol Chem 288(28):20692\u2013701. https:\/\/doi.org\/10.1074\/jbc.M113.485730","journal-title":"J Biol Chem"},{"key":"1812_CR20","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.ijcard.2015.10.221","volume":"203","author":"S Costantino","year":"2016","unstructured":"Costantino S, Paneni F, L\u00fcscher TF, Cosentino F (2016) Pin1 inhibitor Juglone prevents diabetic vascular dysfunction. Int J Cardiol 203:702\u20137. https:\/\/doi.org\/10.1016\/j.ijcard.2015.10.221 (Epub 2015 Oct 30 PMID: 26583846)","journal-title":"Int J Cardiol"},{"issue":"40","key":"1812_CR21","doi-asserted-by":"publisher","first-page":"24255","DOI":"10.1074\/jbc.M115.658559","volume":"290","author":"Y Nakatsu","year":"2015","unstructured":"Nakatsu Y, Iwashita M, Sakoda H, Ono H, Nagata K, Matsunaga Y, Fukushima T, Fujishiro M, Kushiyama A, Kamata H, Takahashi S, Katagiri H, Honda H, Kiyonari H, Uchida T, Asano T (2015) Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the \u03b3 subunit. J Biol Chem 290(40):24255\u201366. https:\/\/doi.org\/10.1074\/jbc.M115.658559","journal-title":"J Biol Chem"},{"issue":"12","key":"1812_CR22","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.1016\/j.celrep.2019.02.066","volume":"26","author":"Y Nakatsu","year":"2019","unstructured":"Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue MK, Mizuno Y, Nakanishi M, Sano T, Yamawaki Y, Kushiyama A, Sakoda H, Fujishiro M, Ryo A, Ono H, Minamino T, Takahashi SI, Ohno H, Yoneda M, Takahashi K, Ishihara H, Katagiri H, Nishimura F, Kanematsu T, Yamada T, Asano T (2019) Prolyl Isomerase Pin1 suppresses thermogenic programs in adipocytes by promoting degradation of transcriptional co-activator PRDM16. Cell Rep 26(12):3221-3230e3. https:\/\/doi.org\/10.1016\/j.celrep.2019.02.066","journal-title":"Cell Rep"},{"issue":"43","key":"1812_CR23","doi-asserted-by":"publisher","first-page":"33018","DOI":"10.1074\/jbc.M110.137836","volume":"285","author":"Y Nakatsu","year":"2010","unstructured":"Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Horike N, Yoneda M, Ohno H, Tsuchiya Y, Kamata H, Tahara H, Isobe T, Nishimura F, Katagiri H, Oka Y, Fukushima T, Takahashi SI, Kurihara H, Uchida T, Asano T (2010) Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing cAMP-responsive element transcriptional activity. J Biol Chem 285(43):33018\u201333027. https:\/\/doi.org\/10.1074\/jbc.M110.137836","journal-title":"J Biol Chem"},{"issue":"4","key":"1812_CR24","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1159\/000235555","volume":"90","author":"YH Lee","year":"2009","unstructured":"Lee YH, Martin JM, Maple RL, Tharp WG, Pratley RE (2009) Plasma amyloid-beta peptide levels correlate with adipocyte amyloid precursor protein gene expression in obese individuals. Neuroendocrinology 90(4):383\u2013390. https:\/\/doi.org\/10.1159\/000235555","journal-title":"Neuroendocrinology"},{"issue":"6","key":"1812_CR25","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1210\/clinem\/dgab098","volume":"106","author":"SE Stinson","year":"2021","unstructured":"Stinson SE, Jonsson AE, Lund MAV, Frithioff-B\u00f8js\u00f8e C, Aas Holm L, Pedersen O, \u00c4ngquist L, S\u00f8rensen TIA, Holst JJ, Christiansen M, Holm JC, Hartmann B, Hansen T (2021) Fasting plasma GLP-1 is associated with overweight\/obesity and cardiometabolic risk factors in children and adolescents. J Clin Endocrinol Metab 106(6):1718\u20131727. https:\/\/doi.org\/10.1210\/clinem\/dgab098","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1812_CR26","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1210\/jc.2015-3885","volume":"101","author":"H Manell","year":"2016","unstructured":"Manell H, Staaf J, Manukyan L, Kristinsson H, Cen J, Stenlid R, Ciba I, Forslund A, Bergsten P (2016) Altered plasma levels of glucagon, GLP-1 and glicentin during OGTT in adolescents with obesity and type 2 diabetes. J Clin Endocrinol Metab 101(3):1181\u20139. https:\/\/doi.org\/10.1210\/jc.2015-3885","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1812_CR27","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1161\/01.atv.20.6.1588","volume":"20","author":"M Carlsson","year":"2000","unstructured":"Carlsson M, Wessman Y, Almgren P, Groop L (2000) High levels of nonesterified fatty acids are associated with increased familial risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 20(6):1588\u201394. https:\/\/doi.org\/10.1161\/01.atv.20.6.1588","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"11","key":"1812_CR28","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1111\/eci.12519","volume":"45","author":"SM Grundy","year":"2015","unstructured":"Grundy SM (2015) Adipose tissue and metabolic syndrome: too much, too little or neither. Eur J Clin Invest 45(11):1209\u201317. https:\/\/doi.org\/10.1111\/eci.12519","journal-title":"Eur J Clin Invest"},{"issue":"4","key":"1812_CR29","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s00125-017-4534-6","volume":"61","author":"LW Johnston","year":"2018","unstructured":"Johnston LW, Harris SB, Retnakaran R, Giacca A, Liu Z, Bazinet RP, Hanley AJ (2018) Association of NEFA composition with insulin sensitivity and beta cell function in the prospective metabolism and islet cell evaluation (PROMISE) cohort. Diabetologia 61(4):821\u2013830. https:\/\/doi.org\/10.1007\/s00125-017-4534-6","journal-title":"Diabetologia"}],"container-title":["Journal of Endocrinological Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01812-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40618-022-01812-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-022-01812-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T12:10:44Z","timestamp":1659960644000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40618-022-01812-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,18]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["1812"],"URL":"https:\/\/doi.org\/10.1007\/s40618-022-01812-8","relation":{},"ISSN":["1720-8386"],"issn-type":[{"value":"1720-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,18]]},"assertion":[{"value":"25 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2022","order":3,"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 they have no conflicts of interest. M.M. is member of the Editorial Board of JENI.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any study on animals. The study research on humans was conducted in line with the Declaration of Helsinky. The Ethical approval was obtained from the Ethics Committee at the \u201cOspedale Pediatrico Bambino Ges\u00f9\u201d (2050_OPBG_2020).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"Written informed consent was obtained from the parents and legal guardians. Patients\u2019 data were treated to guarantee confidentiality.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Both authors have read and agreed to the published article.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}