{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T05:03:35Z","timestamp":1718946215261},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,9,20]],"date-time":"2015-09-20T00:00:00Z","timestamp":1442707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001537","name":"University of Auckland","doi-asserted-by":"publisher","award":["WT098498","HL\u2010102923","HL\u2010102924","HL\u2010102925","HL\u2010102926"],"award-info":[{"award-number":["WT098498","HL\u2010102923","HL\u2010102924","HL\u2010102925","HL\u2010102926"]}],"id":[{"id":"10.13039\/501100001537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT098498"],"award-info":[{"award-number":["WT098498"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet. Med."],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Severe, early\u2010onset insulin resistance in the absence of obesity, hepatic steatosis and dyslipidaemia is frequently attributable to a genetic defect affecting the insulin receptor. We describe a patient with severe insulin resistance in whom insulin receptor mutation analysis was mistakenly recorded as normal. Western blot analysis of skeletal muscle showed reduced insulin receptor protein and led to re\u2010evaluation of the insulin receptor and the discovery of a novel mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>A Niuean women, first evaluated at age 6\u00a0years for severe acanthosis nigricans, hirsutism, poor growth and cognitive impairment, had extremely elevated fasting insulin levels of 10740\u00a0IU\/l (fasting reference range 4\u201324\u00a0IU\/l) and a normal glucose concentration (4.9\u00a0mmol\/l). Diabetes was diagnosed at age 9\u00a0years and metformin treatment introduced. By age 14\u00a0years, she developed refractory hyperglycaemia despite metformin, rosiglitazone and 240\u00a0IU insulin daily. Insulin receptor genetic analysis was documented as normal. At age 23\u00a0years, with a blood glucose concentration of 37\u00a0mmol\/l and an HbA<jats:sub>1c<\/jats:sub> concentration of 116\u00a0mmol\/mol, U500 insulin 2000\u00a0IU\/day was required for glycaemic control. She developed severe proliferative diabetic retinopathy with neovascular glaucoma leading to blindness. There was no renal dysfunction, dyslipidaemia or hepatic steatosis. A muscle biopsy was performed to evaluate the insulin signalling pathway and showed reduced insulin receptor protein. Sequencing of the insulin receptor showed a homozygous p.Val1010Leu missense mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This patient illustrates the use of muscle biopsy in the evaluation of a patient with unexplained severe insulin resistance. This approach may usefully be applied to other cases of severe insulin resistance, where genetic testing for known mutations in the insulin signalling pathway has been negative.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.12707","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T13:24:53Z","timestamp":1422019493000},"update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel mutation in insulin receptor gene identified after muscle biopsy in a Niuean woman with severe insulin resistance"],"prefix":"10.1111","volume":"32","author":[{"given":"R.","family":"Murphy","sequence":"first","affiliation":[{"name":"Department of Medicine University of Auckland Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of New South Wales Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Isaac","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories University of Cambridge Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Neurology Auckland City Hospital Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. K.","family":"Semple","sequence":"additional","affiliation":[{"name":"University of Cambridge Metabolic Research Laboratories University of Cambridge Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,9,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0020"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900909106"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000023464"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.18.5572"},{"key":"e_1_2_8_6_1","unstructured":"Exome Variant Server NHLBI GO Exome Sequencing Project (ESP) Seattle WA.Available athttp:\/\/evs.gs.washington.edu\/EVS\/Last accessed 1 May 2013."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2013.12.006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000133625.73570.54"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/26.3.283"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.12.1465"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-2194"},{"key":"e_1_2_8_12_1","first-page":"315","article-title":"Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis","volume":"119","author":"Semple RK","year":"2009","journal-title":"J Clin Invest"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.5.1240"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc05-1249"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2001.00898.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2010.03810.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2088"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199011153232016"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031952"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096706"}],"container-title":["Diabetic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdme.12707","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dme.12707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:26:33Z","timestamp":1696292793000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dme.12707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,20]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1111\/dme.12707"],"URL":"https:\/\/doi.org\/10.1111\/dme.12707","archive":["Portico"],"relation":{},"ISSN":["0742-3071","1464-5491"],"issn-type":[{"value":"0742-3071","type":"print"},{"value":"1464-5491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,20]]},"assertion":[{"value":"2015-01-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}