Language:
  
[Sign in] [Register]   

EIAab logo

EIAab news detail, please contact eiaab@eiaab.com if you have any questions about online orders and payment.
Galectin-3 deficiency exacerbates hyperglycemia and the endothelial response to diabetes
Update time:2016-09-07 01:06:00   【 Font: Large  Medium Small

Abstract

Background
Diabetes promotes maladaptive changes in the endothelium that lead to its dysfunction and contribute to the vascular pathology of diabetes. We have previously reported the up-regulation of galectin-3, a β-galactoside-binding lectin, in the endothelium and sera of diabetic mice, implicating this molecule in diabetic vasculopathy and suggesting its potential as a biomarker of the disease. Therefore, we sought to assess the role of galectin-3 in the vascular pathology of diabetes.

Methods
Galectin-3 knockout mice (KO) and wild-type mice (WT) were fed either a high-fat diet (HFD) (60 % fat calories) to produce insulin resistant diabetes, or standard chow (12 % fat calories), and their metabolic and endothelial responses were measured. After 8 weeks, the aortic and skeletal muscle endothelia were isolated by fluorescence sorting of CD105+/CD45− cells and comprehensive transcriptional analyses were performed. Transcripts differentially dysregulated by HFD in KO endothelium compared to WT were confirmed by semi-quantitative RT-PCR, and protein expression was determined by immunofluorescence of aortic and muscle tissue. Ingenuity® Pathway Analysis was used to identify pathways up-regulated by HFD in the KO, such as the coagulation cascade, and measurements of blood clotting activity were performed to confirm these results.

Results
KO mice exhibit greater hyperglycemia and impaired glucose tolerance but lower insulin levels on HFD compared to WT. KO mice demonstrate a more robust transcriptional response to HFD in the vascular endothelium compared to WT. Transcripts dysregulated in the KO endothelium after HFD are involved in glucose uptake and insulin signaling, vasoregulation, coagulation, and atherogenesis. One of the most down-regulated transcripts in the endothelium of the KO after HFD was the glucose transporter, Glut4/Slc2a4. GLUT4 immunofluorescence confirmed lower protein abundance in the endothelium and muscle of the HFD-fed KO. Prothrombin time was decreased in the diabetic KO indicating increased coagulation activity.

Conclusions
Galectin-3 deficiency leads to exacerbated metabolic derangement and endothelial dysfunction. The impaired tissue uptake of glucose in KO mice can be attributed to the reduced expression of GLUT4. Enhanced coagulation activity in the diabetic KO suggests a protective role for galectin-3 against thrombosis. These studies demonstrate that galectin-3 deficiency contributes both to the pathogenesis of diabetes and the associated vasculopathy.

Keywords
Endothelial dysfunction Vasculopathy Microarray analysis GLUT4 Type II diabetes

 

Cited products
Source:Cardiovascular diabetology      by Darrow A L, Shohet R V.
Hot Genes
Atf2 ASPRO ACE ALCAM C19orf80 Trap1a KSR2 Gdf5
Top Searches
Ubiquitin-protein ligase Ubiquitin ELISA metalloproteinase Tumor necrosis Asprosin TRAP1A Alpha
Why choose EIAAB
Our products have been quoted by many publications in famous journals such as Cell; Cell Metabolism; Hepatology; Biomaterials.more
Further Information
About us Protein center Bank account Distributors Terms & Conditions Career eiaab.cn

Copyright & copy www.eiaab.com2006-2016 All Rights Reserved    EIAab         Email:eiaab@eiaab.com

Twitter