Vignini Arianna, Nanetti Laura, Moroni Cinzia, Testa Roberto, Sirolla Cristina, Marra Maurizio, Cenerelli Stefano, Gregori Alessandro, Fumelli Daniele, Olivieri Fabiola, Mazzanti Laura, Rabini Rosa Anna
Institute of Biochemistry, School of Medicine, Polytechnical University of Marche, Via P. Ranieri 65, 60131 Ancona, Italy.
Nutr Metab Cardiovasc Dis. 2008 Oct;18(8):553-8. doi: 10.1016/j.numecd.2007.08.001. Epub 2007 Dec 21.
Three NOS isoforms are responsible for nitric oxide production in various tissues. Endothelial constitutive NOS is expressed in vascular endothelium and in platelets, contributing to vascular tone regulation and platelet aggregation. The aim of the present work was to examine eNOS polymorphism, to find a correlation with platelet NO production and degree of insulin resistance (IR) in non-diabetic subjects and in patients affected by type 2 diabetes.
Seventy-one non-diabetic subjects and 37 patients affected by Type 2 diabetes were recruited. The subjects were subdivided into 3 groups as cut-off for the definition of an insulin resistant state: IR non-diabetic subjects, insulin sensitive subjects, and insulin-resistant patients affected by Type 2 diabetes. Plasma glyco-metabolic parameters, platelet nitric oxide production, endothelial nitric oxide synthase (eNOS) gene polymorphism were measured in all subjects enrolled. Significant differences between groups were found in BMI, fasting glycaemia, fructosamine and HbA(1c), triglycerides and HDL cholesterol levels. Evaluating all the subjects, platelet NO production was significantly related with BMI, waist circumference, and triglycerides concentrations, thus suggesting an association between increased platelet NO production, obesity and hypertriglyceridemia, independent of the degree of insulin-resistance.
The modified platelet NO synthesis does not seem to be due to eNOS Glu298Asp polymorphism, while it can be hypothesized that it is caused by an iNOS induction, present in obesity, hypertriglyceridemia and in type 2 diabetes.
三种一氧化氮合酶（NOS）同工型负责在各种组织中产生一氧化氮。内皮型组成型 NOS 在血管内皮和血小板中表达，有助于调节血管张力和血小板聚集。本研究的目的是检测内皮型 NOS（eNOS）基因多态性，以发现非糖尿病患者和 2 型糖尿病患者中血小板一氧化氮产生与胰岛素抵抗（IR）程度之间的相关性。
招募了 71 名非糖尿病患者和 37 名 2 型糖尿病患者。根据胰岛素抵抗状态的定义切点，将受试者分为 3 组：胰岛素抵抗的非糖尿病患者、胰岛素敏感的受试者以及患有 2 型糖尿病的胰岛素抵抗患者。对所有纳入的受试者测量了血浆糖代谢参数、血小板一氧化氮产生、内皮型一氧化氮合酶（eNOS）基因多态性。在体重指数（BMI）、空腹血糖、果糖胺和糖化血红蛋白 A1c（HbA1c）、甘油三酯和高密度脂蛋白胆固醇水平方面，各分组之间存在显著差异。评估所有受试者后发现，血小板一氧化氮产生与 BMI、腰围和甘油三酯浓度显著相关，这表明血小板一氧化氮产生增加、肥胖和高甘油三酯血症之间存在关联，且与胰岛素抵抗程度无关。
血小板一氧化氮合成的改变似乎并非由于 eNOS Glu298Asp 基因多态性，而可以推测是由肥胖、高甘油三酯血症和 2 型糖尿病中存在的诱导型一氧化氮合酶（iNOS）引起的。
