gene expression profiles of beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetesβ细胞丰富组织的基因表达谱获得的激光捕获显微解剖与2型糖尿病的受试者.pdfVIP

Gene Expression Profiles of Beta-Cell Enriched Tissue Obtained by Laser Capture Microdissection from Subjects with Type 2 Diabetes 1 1 2 2 1 1 Lorella Marselli , Jeffrey Thorne , Sonika Dahiya , Dennis C. Sgroi , Arun Sharma , Susan Bonner-Weir , 3 1 Piero Marchetti , Gordon C. Weir * 1 Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and the Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Molecular Pathology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Section of Endocrinology and Metabolism of Organ Transplantation, Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy Abstract Background: Changes in gene expression in pancreatic beta-cells from type 2 diabetes (T2D) should provide insights into their abnormal insulin secretion and turnover. Methodology/Principal Findings: Frozen sections were obtained from cadaver pancreases of 10 control and 10 T2D human subjects. Beta-cell enriched samples were obtained by laser capture microdissection (LCM). RNA was extracted, amplified and subjected to microarray analysis. Further analysis was performed with DNA-Chip Analyzer (dChip) and Gene Set Enrichment Analysis (GSEA) software. There were changes in expression of genes linked to glucotoxicity. Evidence of oxidative stress was provided by upregulation of several metallothionein genes. There were few changes in the major genes associated with cell cycle, apoptosis or endoplasmic reticulum stress. There was differential expression of genes associated with pancreatic regeneration, most