Metformin reduces endothelial cell expression of both the receptor for advanced glycation end products and lectin-like oxidized receptor 1

Ouslimani, Nadjat; Mahrouf, Meriem; Peynet, Jacqueline; Bonnefont‐Rousselot, Dominique; Cosson, Claudine; Legrand, Alain; Beaudeux, Jean-Louis

doi:10.1016/j.metabol.2006.10.010

Cited by 53 publications

(32 citation statements)

References 39 publications

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“…Treatment with metformin restores endothelial function through inhibiting endoplasmic reticulum stress and oxidative stress in obese diabetic mice (Cheang et al, 2014). In cultured bovine aortic endothelial cells, the intracellular antioxidant properties of metformin (10 mM) result in the inhibition of cell expression of both RAGE and lectin-like oxidized receptor 1, possibly through a modulation of redox-sensible nuclear factors such as NF-kB (Ouslimani et al, 2007). Our present data showed that metformin reversed the enhanced ROS generation induced by AGEs (Fig.…”

supporting

confidence: 58%

“…These results indicated that alterations of the K Ca channel both in protein expression and channel activity may be responsible for the beneficial effect of metformin on IK Ca -and SK Ca -mediated relaxation in vivo. However, we cannot exclude other mechanisms concerning the inhibitory effect of metformin on receptor for AGEs (RAGE) and downstream processes (Ouslimani et al, 2007;Ishibashi et al, 2012a,b).…”

mentioning

confidence: 97%

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Metformin Restores Intermediate-Conductance Calcium-Activated K+ Channel– and Small-Conductance Calcium-Activated K+ Channel–Mediated Vasodilatation Impaired by Advanced Glycation End Products in Rat Mesenteric Artery

Zhao

Wang

Yang

et al. 2014

Molecular Pharmacology

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The present study was designed to investigate the effect of metformin on the impairment of intermediate-conductance and small-conductance Ca 21-activated potassium channels (IK Ca and SK Ca )-mediated relaxation in diabetes and the underlying mechanism. The endothelial vasodilatation function of mesenteric arteries was assessed with the use of wire myography. Expression levels of IK Ca and SK Ca and phosphorylated Thr 172 of AMPactivated protein kinase (AMPK) were measured using Western blot technology. The channel activity was observed using a whole-cell patch voltage clamp. Reactive oxygen species (ROS) were measured using dihydroethidium and 29,79-dichlorofluorescein diacetate. Metformin restored the impairment of IK Ca -and SK Camediated vasodilatation in mesenteric arteries from streptozotocininduced type 2 diabetic rats and that from normal rats incubated with advanced glycation end products (AGEs) for 3 hours. In cultured human umbilical vein endothelial cells (HUVECs), 1 mM metformin reversed AGE-induced increase of ROS and attenuated AGEand H 2 O 2 -induced downregulation of IK Ca and SK Ca after longterm incubation (.24 hours). Short-term treatment (3 hours) with 1 mM metformin reversed the decrease of IK Ca and SK Ca currents induced by AGE incubation for 3 hours without changing the channel expression or the AMPK activation in HUVECs. These results are the first to demonstrate that metformin restored IK Ca -and SK Ca -mediated vasodilatation impaired by AGEs in rat mesenteric artery, in which the upregulation of channel activity and protein expression is likely involved.

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supporting

confidence: 58%

mentioning

confidence: 97%

Metformin Restores Intermediate-Conductance Calcium-Activated K+ Channel– and Small-Conductance Calcium-Activated K+ Channel–Mediated Vasodilatation Impaired by Advanced Glycation End Products in Rat Mesenteric Artery

Zhao

Wang

Yang

et al. 2014

Molecular Pharmacology

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“…[37] More interestingly, many agents, such as stains, metformin, and pioglitazone, downregulated LOX-1 expression via the reduction of intracellular superoxide radical generation and inhibition of LDL oxidation. [38][39][40] In the present study, taurine treatment significantly decreased diabetes-induced overexpression of renal LOX-1 protein and gene, simultaneously reduced the renal MDA levels, and restored the renal GSH-Px activities in diabetic rats, suggesting beneficial effects of taurine on early DN may be attributed to the suppression of oxidative stress-induced overexpression of LOX-1 protein and gene in diabetic kidney. The overexpression of ICAM-1, which induces leukocyte infiltration and macrophage recruitment into glomerular, are recognized in DN.…”

Section: Discussionsupporting

confidence: 64%

The Protective Effects of Taurine against Early Renal Injury in STZ-Induced Diabetic Rats, Correlated with Inhibition of Renal LOX-1-Mediated ICAM-1 Expression

Wang

Zhang

et al. 2008

Renal Failure

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Oxidative stress is a key cause in the development of diabetic nephropathy (DN). As a main receptor of oxidized lowdensity lipoprotein (oxLDL), LOX-1 plays an important role in the induction of leukocyte adhesion molecules, such as intercellular cell adhesion molecule-1 (ICAM-1). Taurine (TAU), a potent endogenous antioxidant, showed renoprotective effects in several model animals. This study was designed to determine the renoprotective effect and possible mechanism involved LOX-1 and ICAM-1 expression of taurine in early DN. Six-week-old male Wistar rats were divided into three groups: normal control (NC), diabetes mellitus (DM), and taurine-treated DM (DM+TAU). Diabetes was induced by streptozotocin (STZ, 60 mg/kg, i.p.). After the onset of diabetes, drinking water containing 1% taurine was given to rats in the DM+TAU group. After six weeks of treatment, blood glucose (BG), serum levels of creatinine (sCr) and BUN, and LOX-1 and ICAM-1 expression (protein and gene) in kidney cortices were estimated. Meanwhile, renal malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activities were examined as parameters of oxidative stress in diabetic rats. For DM+TAU rats, when compared with DM rats, the levels of serum BUN, sCr, and renal MDA were reduced, and the activities of renal GSH-Px were increased, but the BG levels were not influenced. Simultaneously, taurine attenuated histopathologic evidence of renal damages and reduced the overexpression of LOX-1 and ICAM-1 in kidney cortices of diabetic rats. In conclusion, taurine showed protective effects against early renal injury in diabetic rats. These renoprotective effects may be partly caused by suppression of oxLDL/LOX-1 system and subsequently ICAM-1 overexpression on renal cortex via its antioxidative property.

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“…Also, an effect of metformin treatment on erythrocyte antioxidative defence enzymes was demonstrated by Pavlovic et al in newly diagnosed, obese type 2 diabetic patients [25]. Furthermore, metformin has been demonstrated to directly decrease hyperglycaemia-driven enhanced ROS production in both bovine and human endothelial cells [26,27]. Finally, a protective action of metformin against oxidative stress could be hypothesized on the basis of its chelating properties toward metals such as copper or iron, involved in the radical-generating Fenton system [28].…”

Section: Discussionmentioning

confidence: 90%

Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects

Formoso

Filippis

Michetti

et al. 2007

Diabetes Metabolism Res

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Metformin reduces endothelial cell expression of both the receptor for advanced glycation end products and lectin-like oxidized receptor 1

Cited by 53 publications

References 39 publications

Metformin Restores Intermediate-Conductance Calcium-Activated K+ Channel– and Small-Conductance Calcium-Activated K+ Channel–Mediated Vasodilatation Impaired by Advanced Glycation End Products in Rat Mesenteric Artery

Metformin Restores Intermediate-Conductance Calcium-Activated K+ Channel– and Small-Conductance Calcium-Activated K+ Channel–Mediated Vasodilatation Impaired by Advanced Glycation End Products in Rat Mesenteric Artery

The Protective Effects of Taurine against Early Renal Injury in STZ-Induced Diabetic Rats, Correlated with Inhibition of Renal LOX-1-Mediated ICAM-1 Expression

Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects

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