Galectin-3 deficiency exacerbates hyperglycemia and the endothelial response to diabetes

摘要: Diabetes promotes maladaptive changes in the endothelium that lead to its dysfunction and contribute vascular pathology of diabetes. We have previously reported up-regulation galectin-3, a β-galactoside-binding lectin, sera diabetic mice, implicating this molecule vasculopathy suggesting potential as biomarker disease. Therefore, we sought assess role galectin-3 Galectin-3 knockout mice (KO) wild-type (WT) were fed either high-fat diet (HFD) (60 % fat calories) produce insulin resistant diabetes, or standard chow (12 % calories), their metabolic endothelial responses measured. After 8 weeks, aortic skeletal muscle endothelia isolated by fluorescence sorting CD105+/CD45− cells comprehensive transcriptional analyses performed. Transcripts differentially dysregulated HFD KO compared WT confirmed semi-quantitative RT-PCR, protein expression was determined immunofluorescence tissue. Ingenuity® Pathway Analysis used identify pathways up-regulated KO, such coagulation cascade, measurements blood clotting activity performed confirm these results. exhibit greater hyperglycemia impaired glucose tolerance but lower levels on WT. demonstrate more robust response after are involved uptake signaling, vasoregulation, coagulation, atherogenesis. One most down-regulated transcripts transporter, Glut4/Slc2a4. GLUT4 abundance HFD-fed KO. Prothrombin time decreased indicating increased activity. deficiency leads exacerbated derangement dysfunction. The tissue can be attributed reduced GLUT4. Enhanced suggests protective for against thrombosis. These studies contributes both pathogenesis diabetes associated vasculopathy.