国际内分泌代谢杂志
國際內分泌代謝雜誌
국제내분비대사잡지
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2012年
6期
376-378
,共3页
替米沙坦%2型糖尿病%细胞周期素依赖性蛋白激酶5%PPARγ
替米沙坦%2型糖尿病%細胞週期素依賴性蛋白激酶5%PPARγ
체미사탄%2형당뇨병%세포주기소의뢰성단백격매5%PPARγ
Telmisartan%Type 2 diabetes mellitus%Cyclin dependent kinase 5%PPARγ
细胞周期素依赖性蛋白激酶(Cdk)5介导的过氧化物酶体增殖物活化受体(PPAR)γ磷酸化通过干扰脂联素等胰岛素敏感性相关细胞因子的基因表达,引起胰岛素抵抗并最终引发2型糖尿病.替米沙坦一方面通过改变PPARγ的蛋白构象使其273位丝氨酸不能与Cdk5结合来调控PPARγ功能；另一方面,作为抑制血管紧张素Ⅱ1型受体阻断剂,替米沙坦通过改善肥胖状态下脂肪组织的炎性反应,直接激活Cdk5.因此,对Cdk5介导的PPARγ磷酸化的抑制可能在替米沙坦预防2型糖尿病中发挥重要作用.
細胞週期素依賴性蛋白激酶(Cdk)5介導的過氧化物酶體增殖物活化受體(PPAR)γ燐痠化通過榦擾脂聯素等胰島素敏感性相關細胞因子的基因錶達,引起胰島素牴抗併最終引髮2型糖尿病.替米沙坦一方麵通過改變PPARγ的蛋白構象使其273位絲氨痠不能與Cdk5結閤來調控PPARγ功能；另一方麵,作為抑製血管緊張素Ⅱ1型受體阻斷劑,替米沙坦通過改善肥胖狀態下脂肪組織的炎性反應,直接激活Cdk5.因此,對Cdk5介導的PPARγ燐痠化的抑製可能在替米沙坦預防2型糖尿病中髮揮重要作用.
세포주기소의뢰성단백격매(Cdk)5개도적과양화물매체증식물활화수체(PPAR)γ린산화통과간우지련소등이도소민감성상관세포인자적기인표체,인기이도소저항병최종인발2형당뇨병.체미사탄일방면통과개변PPARγ적단백구상사기273위사안산불능여Cdk5결합래조공PPARγ공능；령일방면,작위억제혈관긴장소Ⅱ1형수체조단제,체미사탄통과개선비반상태하지방조직적염성반응,직접격활Cdk5.인차,대Cdk5개도적PPARγ린산화적억제가능재체미사탄예방2형당뇨병중발휘중요작용.
The phosphorylation of peroxisome proliferator-activated receptor gamma (PPARγ),which is mediated by cyclin dependent kinase (Cdk) 5,can downregulate the expression of adiponectin (a central regulator of insulin sensitivity in vivo),then cause insulin resistance,even type 2 diabetes mellitus (T2DM).On one hand,telmisartan may alter the conformation/dynamic nature of PPARγ,so that Ser-273 of the protein is no longer modified by Cdk5,and then the phosphorylation of PPARγis inhibited.On the other hand,as an angiotensin Ⅱ type-1 receptor blocker,telmisartan might inactivate Cdk5 directly by protecting the adipose tissue from inflammatory lesion in condition of obesity.Therefore Cdk5-mediated phosphorylation of PPARγ may be involved in the mechanism of prevention of T2DM by telmisartan.
