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急性胆管炎に抗菌薬をどう選択する? (日経BP)

こんにちは、AST専従薬剤師として抗菌薬適正使用に携わっている柏原です。今回は、急性胆管炎に対する薬物治療の考え方や、実際のASTの関わりについて紹介したいと思...

  1. 最前線で新型コロナ対応に当たったキーパー...
  2. 薬局の待合にデジタルサイネージを設置! ...
  3. 夜間頻尿でベオーバが追加処方された患者 ...
  4. 環境負荷に懸念 データセンター、再エネ利...

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Activation of Transient Receptor Potential Channel Vanilloid 4 by DPP-4 (Dipeptidyl Peptidase-4) Inhibitor Vildagliptin Protects Against Diabetic Endothelial Dysfunction.

著者 Gao P , Li L , Wei X , Wang M , Hong Y , Wu H , Shen Y , Ma T , Wei X , Zhang Q , Fang X , Wang L , Yan Z , Du GH , Zheng H , Yang G , Liu D , Zhu Z
Hypertension.2019 Nov 18 ; ():HYPERTENSIONAHA11913778.
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Endothelial dysfunction is an early step to the progression of cardiovascular diseases in diabetes. Apart from their anti-diabetic action, DPP-4 (dipeptidyl peptidase-4) inhibitors also reduce cardiovascular events in diabetic patients. However, the underlying mechanism of the beneficial effect of DPP-4 inhibitor on endothelial function is still obscure. In this study, we intervened type 1 or 2 diabetic model mice with vildagliptin for 4 weeks and measured the vascular reactivity. We found that vildagliptin improved endothelium-dependent vasodilation in diabetic mice independent of GLP-1 (glucagonlike peptide-1), but this effect was blocked by a SIRT1 (Sirtuin 1) inhibitor, Ex527. Mechanistically, vildagliptin-activated Transient Receptor Potential Channel Vanilloid 4 (TRPV4) to promote extracellular calcium uptake in endothelial cells, which activated AMPK (AMP-activated protein kinase)/SIRT1 pathway to counteract hyperglycemia-induced endothelial reactive oxygen species generation and senescence. Vildagliptin directly binds to TRPV4 by forming a hydrogen bond, which is critical to vildagliptin-evoked endothelial calcium intake. Knockout or inhibition of TRPV4 erased the beneficial role of vildagliptin. In addition, activation of SIRT1 by SRT1720 improved endothelial function independent of TRPV4 and reduced TRPV4 transcription to maintain an appropriate calcium level. In summary, our findings prove that vildagliptin protects against hyperglycemia-induced endothelial dysfunction by activating TRPV4-meditaed Ca uptake, which helps to re-understand the mechanism of DPP-4 inhibitors and expand the therapeutic scope.
PMID: 31735085 [PubMed - as supplied by publisher]
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