{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:30:03Z","timestamp":1790227803025,"version":"4.1.0"},"reference-count":16,"publisher":"American Diabetes Association","issue":"3","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,3,1]]},"abstract":"<jats:p>We previously reported a family in which a heterozygous missense mutation in Akt2 led to a dominantly inherited syndrome of insulin-resistant diabetes and partial lipodystrophy. To determine whether genetic variation in AKT2 plays a broader role in human metabolic disease, we sequenced the entire coding region and splice junctions of AKT2 in 94 unrelated patients with severe insulin resistance, 35 of whom had partial lipodystrophy. Two rare missense mutations (R208K and R467W) were identified in single individuals. However, insulin-stimulated kinase activities of these variants were indistinguishable from wild type. In two large case-control studies (total number of participants 2,200), 0 of 11 common single nucleotide polymorphism (SNPs) in AKT2 showed significant association with type 2 diabetes. In a quantitative trait study of 1,721 extensively phenotyped individuals from the U.K., no association was found with any relevant intermediate metabolic trait. In summary, although heterozygous loss-of- function mutations in AKT2 can cause a syndrome of severe insulin resistance and lipodystrophy in humans, such mutations are uncommon causes of these syndromes. Furthermore, genetic variation in and around the AKT2 locus is unlikely to contribute significantly to the risk of type 2 diabetes or related intermediate metabolic traits in U.K. populations.<\/jats:p>","DOI":"10.2337\/db06-0921","type":"journal-article","created":{"date-parts":[[2007,2,27]],"date-time":"2007-02-27T18:14:43Z","timestamp":1172600083000},"page":"714-719","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":59,"title":["Analysis of Genetic Variation in Akt2\/PKB-\u03b2 in Severe Insulin Resistance, Lipodystrophy, Type 2 Diabetes, and Related Metabolic Phenotypes"],"prefix":"10.2337","volume":"56","author":[{"given":"Karen","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge, U.K"},{"name":"Metabolic Disease Group, The Wellcome Trust Sanger Institute, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Kimber","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2019an","family":"Luan","sequence":"additional","affiliation":[{"name":"Medical Research Council Epidemiology Unit, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Soos","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert K.","family":"Semple","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Wareham","sequence":"additional","affiliation":[{"name":"Medical Research Council Epidemiology Unit, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"O\u2019Rahilly","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, University of Cambridge, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ine\u0302s","family":"Barroso","sequence":"additional","affiliation":[{"name":"Metabolic Disease Group, The Wellcome Trust Sanger Institute, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031209203365600_R1","doi-asserted-by":"crossref","unstructured":"Taniguchi CM, Emanuelli B, Kahn CR: Critical nodes in signalling pathways: insights into insulin action. 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