人血管平滑肌细胞表达一种组成型一氧化氮合酶，胰岛素迅速激活，从而增加鸟苷3':5'-环单磷酸和腺苷3':5'-环单磷酸的浓度。

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Trovati M, Massucco P, Mattiello L, Costamagna C, Aldieri E, cavot F, Anfossi G, Bosia A, Ghigo D

人血管平滑肌细胞表达一种组成型一氧化氮合酶，胰岛素迅速激活，从而增加鸟苷3':5'-环单磷酸和腺苷3':5'-环单磷酸的浓度。

糖尿病杂志1999 7月;42(7):831-9。

PubMed ID

10440125 (PubMed视图

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摘要

目的/假设:胰岛素孵育人血管平滑肌细胞(hVSMC) 120 min可增加鸟苷3':5'-环单磷酸(cGMP)和腺苷3':5'-环单磷酸(cAMP)，且这些作用可通过抑制一氧化氮合酶(NOS)而被阻断。这些数据表明，胰岛素激活了构成性Ca2+依赖性NOS (cNOS)，目前尚未在hVSMC中描述。为了验证这一假设，我们在hVSMC中评估:i)胰岛素诱导的两种环核苷酸增强的动力学;ii)一氧化氮(NO)增加两种环核苷酸的能力;iii)不涉及胰岛素对两种环核苷酸的短期影响;iv)胰岛素在几分钟内增加NO生成的能力;v)存在cNOS活动;vi) cNOS mRNA的表达。方法:在胰岛素、NO供体和Ca2+离子载体离子霉素孵育的hVSMC中，我们测量cAMP和cGMP (RIA);在胰岛素和离子霉素孵育的hVSMC中，我们测量NO，评估L-(3H)-精氨酸产生L-(3H)-瓜氨酸; by northern blot hybridization, we measured the expression of cNOS mRNA. RESULTS: i) By incubating hVSMC with 2 nmol/l insulin for 0-240 min, we observed an increase of both cGMP and cAMP (ANOVA: p = 0.0001). Cyclic GMP rose from 0.74 +/- 0.01 to 2.62 +/- 0.10 pmol/10(6) cells at 30 min (p = 0.0001); cAMP rose from 0.9 +/- 0.09 to 11.65 +/- 0.74 pmol/10(6) cells at 15 min (p=0.0001). ii) Sodium nitroprusside (100 mol/l) and glyceryltrinitrate (100 micromol/l) increased both cGMP and cAMP (p = 0.0001). iii) The effects of insulin on cyclic nucleotides were blocked by NOS inhibition. iv) An increase of NO was observed by incubating hVSMC for 5 min with 2 nmol/l insulin (p = 0.0001). v) Ionomycin (1 micromol/l) enhanced NO production (p = 0.0001) and increased both cyclic nucleotides (p = 0.0001). vi) hVSMC expressed mRNA of cNOS. CONCLUSION/INTERPRETATION: Human VSMC express cNOS, which is rapidly activated by insulin with a consequent increase of both cGMP and cAMP, suggesting that insulin-induced vasodilation in vivo is not entirely endothelium-mediated.

引用本文的药物库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
瓜氨酸	一氧化氮合酶，内皮细胞	蛋白质	人类	未知的	不可用	细节