Glimepiride upregulates eNOS activity and inhibits cytokine‐induced NF‐κB activation through a phosphoinoside 3‐kinase–Akt‐dependent pathway

Jojima, Teruo; Suzuki, Kunihiro; Hirama, Noriyuki; Uchida, Kohsuke; Hattori, Yoshiyuki

doi:10.1111/j.1463-1326.2008.00923.x

Cited by 31 publications

(21 citation statements)

References 20 publications

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“…[50][51][52][53] It would be interesting to determine whether glimepiride facilitates IPC by activating the PI3K-Akt pathway in the diabetic heart. In this regard, glimepiride has been reported to activate Akt in both coronary endothelial cells, 43 human umbilical vein endothelial cells, 44 and adipocytes. 45 Furthermore, it has been reported that the peroxisome proliferator-activated receptor (PPAR)-g agonist, rosiglitazone, also has the ability to cardioprotect the diabetic rat heart through the activation of Akt.…”

Section: Discussionmentioning

confidence: 99%

“…38,39 Importantly, the antidiabetic sulfonylurea, glibenclamide, which is used less frequently nowadays, is known to block the cardioprotective effects of IPC by acting as an antagonist of the mitochondrial ATP-dependent potassium channel. 40,41 Interestingly, the sulfonylurea, glimepiride, which does not block IPC cardioprotection, 42 has been reported to activate Akt when administered to the endothelial cells, 43 human umbilical vein endothelial cells, 44 and adipocytes. 45 In the present study, we investigate whether pretreatment with glimepiride can facilitate IPC in the diabetic heart.…”

Section: Introductionmentioning

confidence: 99%

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Glimepiride Treatment Facilitates Ischemic Preconditioning in the Diabetic Heart

Hausenloy

Wynne

Mocanu

et al. 2012

J Cardiovasc Pharmacol Ther

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Aims: The diabetic heart is resistant to the myocardial infarct-limiting effects of ischemic preconditioning (IPC). This may be in part due to the downregulation of the phosphatidylinositol 3 0 -kinase-Akt pathway, an essential component of IPC protection. We hypothesized that treating the diabetic heart with the sulfonylurea, glimepiride, which has been reported to activate Akt, may lower the threshold required to protect the diabetic heart by IPC. Methods: Goto-Kakizaki rats (a type II lean model of diabetes) received glimepiride (20 mg/kg per d, by oral gavage) or vehicle for (a) 3 months (chronic treatment) or (b) 24 hours (subacute treatment). In the third group, glimepiride (10 mmol/L) was administered only to the isolated hearts on the Langendorff apparatus (acute treatment). All hearts were subjected to 35 minutes ischemia and 120 minutes reperfusion ex vivo, at the end of which infarct size was determined by tetrazolium staining. Preconditioning treatment comprised 1 (IPC-1) or 3 (IPC-3) cycles of 5 minutes global ischemia and 10 minutes reperfusion. Results: The diabetic heart was found to be resistant to IPC such that 3-IPC cycles, instead of the usual 1-IPC cycle, were required for cardioprotection. However, pretreatment with glimepiride lowered the threshold for IPC such that both 1 and 3 cycles of IPC elicited cardioprotection: chronic glimepiride treatment (IPC-1 31.9% + 3.8% and IPC-3 33.5% + 2.4% vs 43.9% + 1.4% control, P < .05; N > 6 per group); subacute glimepiride treatment (IPC-1 31.1% + 3.0% and IPC-3 29.3% + 3.3% vs 42.2% + 2.3% control, P < .05 N > 6 per group); and acute glimepiride treatment (IPC-1 28.2% + 3.7% and IPC-3 24.6% + 5.4% vs 41.9% + 5.4% control, P < .05; N > 6 per group). This effect of glimepiride was independent of changes in blood glucose. Conclusions: We report for the first time that glimepiride treatment facilitates the cardioprotective effect elicited by IPC in the diabetic heart.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glimepiride Treatment Facilitates Ischemic Preconditioning in the Diabetic Heart

Hausenloy

Wynne

Mocanu

et al. 2012

J Cardiovasc Pharmacol Ther

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“…Endothelin receptor type B ( EDNRB ) gene is located on 13q22, encoding a nonselective endothelin B receptor (ET B R) which belongs to a super-family of G-protein coupled receptor that mediates endothelins (ETs) [7]. ET B R is able to promote the production of neural crest cell-specific lineage, and thus it is related to the occurrence of Hirschsprung’s disease [8] that is a blockage in the colon.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of EDNRB promoter contributes to the risk of colorectal cancer

et al. 2013

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ObjectiveColorectal cancer (CRC) is one of the most common digestive malignancies in the world. EDNRB is a new candidate tumor suppressor gene which is often down-regulated or even silenced by promoter hypermethylation in various human cancers. However, the function of EDNRB gene in CRC remains unknown. In this study, we examined the expression and DNA methylation of EDNRB in CRC tissues.MethodsA total of 42 paired CRC and adjacent normal tissue samples were used to determine mRNA levels and DNA methylation status of EDNRB gene by qRT-PCR and methylation-specific PCR (MSP), respectively.ResultsOur study showed that EDNRB promoter hypermethylation was more frequently in CRC tissues than in the normal tissues (92.86 versus 59.52, p = 0.001). Consequently, significantly lower level of EDNRB mRNA was found in CRC tumor samples than in normal samples (0.31 ± 0.91 versus 0.70 ± 1.18, p = 0.032).ConclusionsOur results suggested that EDNRB promoter hypermethylation might downregulate its gene expression in CRC, and thus played an important role in the development of CRC.The virtual slideThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7420980471113303

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“…Metformin and sulfonylurea drugs are popular anti-diabetic drugs that have been well described to reduce plasma glucose levels and improve circulating HDL and triglycerides [60]. Both classes of drugs are known to stimulate Akt phosphorylation and may therefore also block cellular autophagy [61,62]. This may suggest that augmentation of insulin receptor signaling and inhibition of cellular autophagy may positively affect both glucose and lipoprotein metabolism.…”

Section: Resultsmentioning

confidence: 99%

Purinergic Signaling, Dyslipidemia and Inflammatory Disease

Sparks

Chatterjee

2012

Cell Physiol Biochem

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Metabolic syndrome is a compound obesity disorder, wherein the abnormal metabolism of glucose and lipid is associated with the development of chronic inflammatory diseases. The prevalence of this disease is increasing in the developed world, but the causative linkage between these metabolic disorders has remained obscure. Metabolic disease may be associated with chronic nucleotide secretion, purinergic signaling and activation of inflammatory pathways. Purinergic signaling has been implicated in impaired glucose metabolism and inflammatory disease and may contribute to dyslipidemia. Our research shows that purinergic signaling disrupts hepatic lipoprotein metabolism by blocking insulin receptor signaling and by activating cellular autophagic pathways. Chronic stimulation of purinergic signaling may therefore be causative to glucose and lipid metabolic disorders and associated with the development of cardiovascular disease.

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Glimepiride upregulates eNOS activity and inhibits cytokine‐induced NF‐κB activation through a phosphoinoside 3‐kinase–Akt‐dependent pathway

Abstract: These data suggest that glimepiride might be a preferable sulphonylurea agent in the setting of type 2 diabetes and vascular disease because it may have protective effects on vascular endothelial cells.

Cited by 31 publications

References 20 publications

Glimepiride Treatment Facilitates Ischemic Preconditioning in the Diabetic Heart

Glimepiride Treatment Facilitates Ischemic Preconditioning in the Diabetic Heart

Hypermethylation of EDNRB promoter contributes to the risk of colorectal cancer

Purinergic Signaling, Dyslipidemia and Inflammatory Disease

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