格列美脲通过一种不依赖小窝蛋白-1但依赖Akt的机制激活内皮型一氧化氮合酶。

Glimepiride activates eNOS with a mechanism Akt but not caveolin-1 dependent.

作者信息

Salani Barbara, Repetto Silvia, Cordera Renzo, Maggi Davide

机构信息

Department of Endocrinology and Metabolism (Di.S.E.M), University of Genova, Genova, Italy.

出版信息

Biochem Biophys Res Commun. 2005 Sep 30;335(3):832-5. doi: 10.1016/j.bbrc.2005.07.149.

DOI:10.1016/j.bbrc.2005.07.149

PMID:16099429

Abstract

Insulin stimulates caveolin-1 and eNOS phosphorylation. The sulfonylurea glimepiride mimics several insulin actions by mechanisms that are poorly understood. Glimepiride induces caveolin-1 phosphorylation and activates PI3K and Akt in rat adipocytes. In this paper, we investigated the effect of glimepiride on eNOS activation in human endothelial cells. We found that glimepiride induces caveolin-1 and eNOS phosphorylation. To better understand the role of caveolin-1 in glimepiride action, we downregulated caveolin-1 expression by specific siRNA transfection. Caveolin-1 silencing did not change eNOS and Akt phosphorylation induced by glimepiride. On the contrary, LY294002, a specific PI3K inhibitor, blocked eNOS serine 1177 phosphorylation. These findings suggest that glimepiride induces eNOS phosphorylation in endothelial cells through an Akt-dependent mechanism, not regulated by caveolin-1.

摘要

胰岛素刺激小窝蛋白-1和内皮型一氧化氮合酶（eNOS）磷酸化。磺脲类药物格列美脲通过人们了解甚少的机制模拟多种胰岛素作用。格列美脲可诱导大鼠脂肪细胞中小窝蛋白-1磷酸化，并激活磷脂酰肌醇-3激酶（PI3K）和蛋白激酶B（Akt）。在本文中，我们研究了格列美脲对人内皮细胞中eNOS激活的影响。我们发现格列美脲可诱导小窝蛋白-1和eNOS磷酸化。为了更好地理解小窝蛋白-1在格列美脲作用中的作用，我们通过特异性小干扰RNA（siRNA）转染下调小窝蛋白-1的表达。小窝蛋白-1沉默并未改变格列美脲诱导的eNOS和Akt磷酸化。相反，特异性PI3K抑制剂LY294002可阻断eNOS丝氨酸1177磷酸化。这些发现表明，格列美脲通过Akt依赖的机制诱导内皮细胞中eNOS磷酸化，不受小窝蛋白-1调控。