General Information:

Id: 6,520
Diseases: Cardiomyopathy, diabetic
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Bos taurus
article
Reference: Ouslimani N et al.(2007) Metformin reduces endothelial cell expression of both the receptor for advanced glycation end products and lectin-like oxidized receptor 1 Metab. Clin. Exp. 56: 308-313 [PMID: 17292717]

Interaction Information:

Comment Beyond its antihyperglycemic action, the antidiabetic oral drug metformin possesses antioxidant properties that may contribute to improve the cardiovascular deleterious effects of the diabetic disease. The study explored whether metformin could modulate the redox-sensible expression of receptor for advanced glycation end products (RAGE) and lectin-like oxidized receptor 1 (LOX-1), 2 endothelial membrane receptors involved in the arterial endothelial dysfunction observed in diabetes. Bovine aortic endothelial cells, either unstimulated or activated by high levels of glucose (30 mmol/L) or advanced glycation end products, were incubated for 72 hours with metformin at therapeutically relevant concentrations. Metformin was shown to reduce, in dose-dependent manner, such expression of the 2 receptors, both in stimulated (by either glucose or advanced glycation end products) and in unstimulated cells. The effect of metformin was associated with a decrease in intracellular reactive oxygen species. Taken together, the results suggest that the intracellular antioxidant properties of metformin may result in the inhibition of cell expression of both RAGE and LOX-1, possibly through a modulation of redox-sensible nuclear factors such as nuclear factor kappaB, that were shown to be involved in such receptor cell expression.
Formal Description
Interaction-ID: 62006

drug/chemical compound

Metformin

decreases_expression of

gene/protein

AGER

in aortic endothelial cells
Drugbank entries Show/Hide entries for Metformin
Comment Beyond its antihyperglycemic action, the antidiabetic oral drug metformin possesses antioxidant properties that may contribute to improve the cardiovascular deleterious effects of the diabetic disease. The study explored whether metformin could modulate the redox-sensible expression of receptor for advanced glycation end products (RAGE) and lectin-like oxidized receptor 1 (LOX-1), 2 endothelial membrane receptors involved in the arterial endothelial dysfunction observed in diabetes. Bovine aortic endothelial cells, either unstimulated or activated by high levels of glucose (30 mmol/L) or advanced glycation end products, were incubated for 72 hours with metformin at therapeutically relevant concentrations. Metformin was shown to reduce, in dose-dependent manner, such expression of the 2 receptors, both in stimulated (by either glucose or advanced glycation end products) and in unstimulated cells. The effect of metformin was associated with a decrease in intracellular reactive oxygen species. Taken together, the results suggest that the intracellular antioxidant properties of metformin may result in the inhibition of cell expression of both RAGE and LOX-1, possibly through a modulation of redox-sensible nuclear factors such as nuclear factor kappaB, that were shown to be involved in such receptor cell expression.
Formal Description
Interaction-ID: 62007

drug/chemical compound

Metformin

decreases_expression of

gene/protein

OLR1

in aortic endothelial cells
Drugbank entries Show/Hide entries for Metformin
Comment Stimulation of cells with advanced glycation end products (AGE)-albumin led to a sharp increase of LOX-1 expression. The simultaneous incubation of cells with AGE-albumin and metformin inhibited such increase in the receptor expression in a concentration-dependent manner.
Formal Description
Interaction-ID: 62008

drug/chemical compound

Advanced glycation end-product

increases_expression of

gene/protein

OLR1

in aortic endothelial cells
Comment High levels of glucose for 72 hours resulted in a significant enhancement in LOX-1 cell expression that was at least partly inhibited by the simultaneous incubation of metformin. As previously observed, the inhibitory effect of metformin on glucose-induced LOX-1 expression appeared to be concentration-dependent.
Formal Description
Interaction-ID: 62009

phenotype

hyperglycemia

increases_expression of

gene/protein

OLR1

in aortic endothelial cells
Comment Stimulation of cells by advanced glycation end products (AGE)-albumin, but not by high levels of glucose, led to a sharp increase of RAGE expression. The simultaneous incubation of cells with AGE-albumin and metformin inhibited such increase in the receptor expression in a concentration-dependent manner.
Formal Description
Interaction-ID: 62010

drug/chemical compound

Advanced glycation end-product

increases_expression of

gene/protein

AGER

in aortic endothelial cells
Comment Stimulation of cells by advanced glycation end products (AGE)-albumin, but not by high levels of glucose, led to a sharp increase of RAGE expression. The simultaneous incubation of cells with AGE-albumin and metformin inhibited such increase in the receptor expression in a concentration-dependent manner.
Formal Description
Interaction-ID: 62011

phenotype

hyperglycemia

NOT increases_expression of

gene/protein

AGER

in aortic endothelial cells