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Genetic studies in Pima Indians have linked acyl\u2010CoA dehydrogenase 10 (<jats:italic>ACAD10<\/jats:italic>) gene polymorphisms, among others, to this predisposition. The gene codes for a protein with a C\u2010terminus region that is structurally similar to members of a family of flavoenzymes\u2014the acyl\u2010CoA dehydrogenases (ACADs)\u2014that catalyze \u03b1,\u03b2\u2010dehydrogenation reactions, including the first step in mitochondrial FAO (FAO), and intermediary reactions in amino acids catabolism. Dysregulation of FAO and an increase in plasma acylcarnitines are recognized as important in the pathophysiology of IR and T2DM. To investigate the deficiency of <jats:italic>ACAD10<\/jats:italic> as a monogenic risk factor for T2DM in human, an <jats:italic>Acad<\/jats:italic>\u2010deficient mouse was generated and characterized. The deficient mice exhibit an abnormal glucose tolerance test and elevated insulin levels. Blood acylcarnitine analysis shows an increase in long\u2010chain species in the older mice. Nonspecific variable pattern of elevated short\u2010terminal branch\u2010chain acylcarnitines in a variety of tissues was also observed. <jats:italic>Acad10<\/jats:italic> mice accumulate excess abdominal adipose tissue, develop an early inflammatory liver process, exhibit fasting rhabdomyolysis, and have abnormal skeletal muscle mitochondria. Our results identify <jats:italic>Acad10<\/jats:italic> as a genetic determinant of T2DM in mice and provide a model to further investigate genetic determinants for insulin resistance in humans.<\/jats:p>","DOI":"10.1007\/s10545-017-0013-y","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T14:55:35Z","timestamp":1485269735000},"page":"49-57","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Investigating the link of <i>ACAD10<\/i> deficiency to type 2 diabetes mellitus"],"prefix":"10.1002","volume":"41","author":[{"given":"Kaitlyn","family":"Bloom","sequence":"first","affiliation":[{"name":"Department of Pediatrics, School of Medicine University of Pittsburgh 4401 Penn Avenue Pittsburgh PA 15224 USA"},{"name":"Graduate School of Public Health University of Pittsburgh Pittsburgh PA 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