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the effects of GLP-1 on SIRT1 and on the related metabolic pathways in vascular endothelial cells: potential effects on vascular injury in diabetic patients
| Content Provider | Semantic Scholar |
|---|---|
| Author | Macchini, Luisa |
| Copyright Year | 2012 |
| Abstract | Background: Incretin therapy may have a potential protective role in the treatment of diabetes associated with the cardiovascular comorbidities. GLP-1 may have beneficial effects in the endothelium and in the cardiac tissue although the molecular mechanisms by which GLP-1 exerts these actions are still unknown. Recently, it has been demonstrated that SIRT1, a NAD’+ deacetylase protein, has a protective role on vascular damage in diabetes by reducing oxidative stress. In several cells and in animal models of diabetes SIRT1 gene expression is reduced. Therefore, SIRT1 may represent a new therapeutic target in the prevention of macrovascular complications of diabetes. Aim: To investigate the effects of GLP-1 on SIRT1 gene expression in human umbelical vein endotelial cells (HUVEC) grown at normal and high glucose. Furthermore, we explored the molecular pathways by which GLP-1 may regulate SIRT1 gene expression. Methods: HUVEC were cultured at 5.5 mM o 20 mM glucose in the presence/ absence of two GLP-1 peptides: GLP-1(7-37) and GLP-1(9-36)NH2. Gene expression of SIRT1 was assessed by RT-PCR real time. Akt, AMPK and ERK phosphorylation were measured by Western Blot. Results: SIRT1 gene expression was significantly reduced in HUVEC grown at 20mM in comparison to cells grown at 5.5 mM of glucose. The treatment of cells with GLP-1(7-37) or with GLP-1(9-36)NH2 increased SIRT1 gene expression at 20mM glucose but not at 5.5 mM glucose. Furthermore, GLP-1(7-37) e GLP-1(9-36)NH2 enhanced two different intracellular pathways: GLP-1(7-37) stimulated Akt while GLP-1(9-36)NH2 activated AMPK. Conclusions: SIRT1 is a new and promising therapeutic target for diabetes. The increase of SIRT1 expression by GLP-1 peptides opens new perspectives for the use of incretin therapy in the prevention of diabetic macrovascular complications. Furthermore, the evidence of different GLP-1-activated pathways allows us to hypothesize different mechanisms in the regulation of the expression of SIRT1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://paduaresearch.cab.unipd.it/4458/2/Tesi_Macchini.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
