gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives differential regulation of insulin signaling pathways基因表达在2型糖尿病患者骨骼肌活检和亲戚微分调节胰岛素信号通路.pdfVIP

Gene Expression in Skeletal Muscle Biopsies from People with Type 2 Diabetes and Relatives: Differential Regulation of Insulin Signaling Pathways 1 2 2 2 1 Jane Palsgaard *, Charlotte Brøns , Martin Friedrichsen , Helena Dominguez , Maja Jensen , Heidi 2 2 2 3 1 2 Storgaard , Camilla Spohr , Christian Torp-Pedersen , Rehannah Borup , Pierre De Meyts , Allan Vaag 1 Receptor Systems Biology Laboratory, Hagedorn Research Institute, Novo Nordisk, Gentofte, Denmark, 2 Steno Diabetes Center, Gentofte, Denmark, 3 Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Abstract Background: Gene expression alterations have previously been associated with type 2 diabetes, however whether these changes are primary causes or secondary effects of type 2 diabetes is not known. As healthy first degree relatives of people with type 2 diabetes have an increased risk of developing type 2 diabetes, they provide a good model in the search for primary causes of the disease. Methods/Principal Findings: We determined gene expression profiles in skeletal muscle biopsies from Caucasian males with type 2 diabetes, healthy first degree relatives, and healthy controls. Gene expression was measured using Affymetrix Human Genome U133 Plus 2.0 Arrays covering the entire human genome. These arrays have not previously been used for this type of study. We show for the first time that genes involved in insulin signaling are significantly upregulated in first degree relatives and significantly downregulated in people with type 2 diabetes. On the individual gene level, 11 genes