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In addition, patients with mitochondrial diseases usually manifest systemic metabolic disorder. However, it is unclear how mitochondrial dysfunction in adipocytes affects the regulation of glucose homeostasis. In this study, we induced mitochondrial dysfunction and overproduction of reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) by addition of respiratory inhibitors oligomycin A and antimycin A and by knockdown of mitochondrial transcription factor A (mt<jats:styled-content style=\"fixed-case\">TFA<\/jats:styled-content>), respectively. We found an attenuation of the insulin response as indicated by lower glucose uptake and decreased phosphorylation of <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>kt upon insulin stimulation of adipocytes with mitochondrial dysfunction. Furthermore, the expression of glucose transporter 4 (<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>lut4) and secretion of adiponectin were decreased in adipocytes with increased <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> generated by defective mitochondria. Moreover, the severity of insulin insensitivity was correlated with the extent of mitochondrial dysfunction. These results suggest that higher intracellular <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> levels elicited by mitochondrial dysfunction resulted in impairment of the function of adipocytes in the maintenance of glucose homeostasis through attenuation of insulin signaling, downregulation of Glut4 expression, and decrease in adiponectin secretion. Our findings substantiate the important role of mitochondria in the regulation of glucose homeostasis in adipocytes and also provide a molecular basis for the explanation of the manifestation of diabetes mellitus or insulin insensitivity in a portion of patients with mitochondrial diseases such as <jats:styled-content style=\"fixed-case\">MELAS<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">MERRF<\/jats:styled-content> syndrome.<\/jats:p>","DOI":"10.1111\/febs.12096","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T15:59:40Z","timestamp":1355846380000},"page":"1039-1050","source":"Crossref","is-referenced-by-count":146,"title":["Mitochondrial dysfunction leads to impairment of insulin sensitivity and adiponectin secretion in adipocytes"],"prefix":"10.1111","volume":"280","author":[{"given":"Chih\u2010Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology National 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