{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:26:12Z","timestamp":1771464372403,"version":"3.50.1"},"reference-count":23,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":4172,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,7,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 mg\/day in younger girls and 850 mg\/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P &amp;lt; 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1-year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P &amp;lt; 0.005).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc09-1750","type":"journal-article","created":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T03:55:22Z","timestamp":1270094122000},"page":"1544-1548","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":23,"title":["A Single Nucleotide Polymorphism in <i>STK11<\/i> Influences Insulin Sensitivity and Metformin Efficacy in Hyperinsulinemic Girls With Androgen Excess"],"prefix":"10.2337","volume":"33","author":[{"given":"Abel","family":"L\u00f3pez-Bermejo","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Dr. Josep Trueta Hospital, Girona, Spain;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Hospital Sant Joan de D\u00e9u, University of Barcelona, Barcelona, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas, Instituto de Salud Carlos III del Ministerio de Ciencia e Innovaci\u00f3n, Madrid, Spain;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Hospital Sant Joan de D\u00e9u, University of Barcelona, Barcelona, Spain;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"de Zegher","sequence":"additional","affiliation":[{"name":"Department of Woman and Child, University of Leuven, Leuven, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Hospital Sant Joan de D\u00e9u, University of Barcelona, Barcelona, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas, Instituto de Salud Carlos III del Ministerio de Ciencia e Innovaci\u00f3n, Madrid, Spain;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2010,3,31]]},"reference":[{"key":"2022031302592328100_B1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1126\/science.286.5439.487","article-title":"Pharmacogenomics: translating functional genomics into rational therapeutics","volume":"286","author":"Evans","year":"1999","journal-title":"Science"},{"key":"2022031302592328100_B2","first-page":"2434","article-title":"A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain","volume":"85","author":"Asunci\u00f3n","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B3","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.fertnstert.2008.06.035","article-title":"The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report","volume":"91","author":"Azziz","year":"2009","journal-title":"Fertil Steril"},{"key":"2022031302592328100_B4","first-page":"3526","article-title":"Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche","volume":"85","author":"Ib\u00e1\u00f1ez","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B5","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2165\/00148581-200608050-00004","article-title":"Polycystic ovary syndrome in adolescents: current and future treatment options","volume":"8","author":"Mastorakos","year":"2006","journal-title":"Paediatr Drugs"},{"key":"2022031302592328100_B6","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1210\/jcem.83.10.5205","article-title":"Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth","volume":"83","author":"Ib\u00e1\u00f1ez","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B7","doi-asserted-by":"crossref","first-page":"5702","DOI":"10.1210\/jc.2002-020926","article-title":"Anovulation in eumenorrheic, nonobese adolescent girls born small for gestational age: insulin sensitization induces ovulation, increases lean body mass, and reduces abdominal fat excess, dyslipidemia, and subclinical hyperandrogenism","volume":"87","author":"Ib\u00e1\u00f1ez","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jpeds.2003.08.015","article-title":"Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome","volume":"144","author":"Ib\u00e1\u00f1ez","year":"2004","journal-title":"J Pediatr"},{"key":"2022031302592328100_B9","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1210\/jc.2008-0013","article-title":"Metformin treatment for four years to reduce total and visceral fat in low birth weight girls with precocious pubarche","volume":"93","author":"Ib\u00e1\u00f1ez","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ceb.2005.01.006","article-title":"New roles for the LKB1\u2192 AMPK pathway","volume":"17","author":"Hardie","year":"2005","journal-title":"Curr Opin Cell Biol"},{"key":"2022031302592328100_B11","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1172\/JCI13505","article-title":"Role of AMP-activated protein kinase in mechanism of metformin action","volume":"108","author":"Zhou","year":"2001","journal-title":"J Clin Invest"},{"key":"2022031302592328100_B12","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/sj.emboj.7600110","article-title":"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK\/PAR-1","volume":"23","author":"Lizcano","year":"2004","journal-title":"EMBO J"},{"key":"2022031302592328100_B13","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1126\/science.1120781","article-title":"The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin","volume":"310","author":"Shaw","year":"2005","journal-title":"Science"},{"key":"2022031302592328100_B14","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1053\/j.gastro.2006.07.032","article-title":"Neither LKB1 nor AMPK are the direct targets of metformin","volume":"131","author":"Hardie","year":"2006","journal-title":"Gastroenterology"},{"key":"2022031302592328100_B15","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1210\/jc.2007-1736","article-title":"Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene","volume":"93","author":"Legro","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B16","first-page":"2283","article-title":"Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche","volume":"82","author":"Ib\u00e1\u00f1ez","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B17","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1210\/jcem-21-11-1440","article-title":"Clinical assessment of body hair growth in women","volume":"21","author":"Ferriman","year":"1961","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B18","first-page":"1599","article-title":"Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism","volume":"76","author":"Iba\u00f1ez","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031302592328100_B19","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1530\/EJE-07-0261","article-title":"Flutamide metformin for post-menarcheal girls with preclinical ovarian androgen excess: evidence for differential response by androgen receptor genotype","volume":"157","author":"Ong","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"2022031302592328100_B20","volume-title":"Patrones de crecimiento y desarrollo en Espa\u00f1a. Atlas de gr\u00e1ficas y tablas. Centro Andrea Prader. Zaragoza 1980\u20132002","author":"Ferr\u00e1ndez-Long\u00e1s","year":"2004"},{"key":"2022031302592328100_B21","first-page":"277","article-title":"Intron-mediated regulation of gene expression","volume":"326","author":"Rose","year":"2008","journal-title":"Curr Top Microbiol Immunol"},{"key":"2022031302592328100_B22","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1042\/CS20080066","article-title":"AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease","volume":"116","author":"Wong","year":"2009","journal-title":"Clin Sci (Lond)"},{"key":"2022031302592328100_B23","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1210\/jc.2004-0463","article-title":"Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome: effects of prepubertal initiation and postpubertal discontinuation of metformin treatment","volume":"89","author":"Ib\u00e1\u00f1ez","year":"2004","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/33\/7\/1544\/608406\/zdc00710001544.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/33\/7\/1544\/608406\/zdc00710001544.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T07:17:20Z","timestamp":1647155840000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/33\/7\/1544\/39390\/A-Single-Nucleotide-Polymorphism-in-STK11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,31]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2010,3,31]]},"published-print":{"date-parts":[[2010,7,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc09-1750","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,31]]}}}