Hypertension and insulin resistance:: Role of peroxisome proliferator-activated receptor γ
Hypertension and insulin resistance:: Role of peroxisome proliferator-activated receptor γ
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DOI：
10.1046/j.1440-1681.1999.03082.x
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发表时间：
1999-07-01
影响因子：
2.9
通讯作者：
Naka, K
中科院分区：
文献类型：
--
作者：
Itoh, H;Doi, K;Naka, K
1.胰岛素抵抗已被强调为高血压、糖尿病、糖尿病和肥胖症的常见致病因素，所有这些都被认为是同时发生的;并且一个独特的临床实体被定义为“多风险因素综合征”。最近，一类新的抗糖尿病药物噻唑烷二酮类（TZD）已经开发出来，并已被证明通过结合和激活核受体过氧化物酶体增殖物激活受体（PPAR）γ来改善胰岛素抵抗。克隆了大鼠PPAR γ 1和γ 2的cDNA，并检测了大鼠成熟脂肪细胞中PPAR γ的基因调控。过氧化氢是一种氧自由基，被认为是多种危险因素的共同细胞内信号，可有效下调大鼠成熟脂肪细胞中PPAR γ mRNA的表达。肿瘤坏死因子（TNF）-α被认为在肥胖诱导的非胰岛素依赖型糖尿病中发挥作用，并增加氧化应激，也抑制了PPAR γ的表达5。噻唑烷二酮类药物剂量依赖性地恢复TNF-α诱导的PPAR γ mRNA表达下调。TZD对PPAR γ表达的调节可能是TZD改善胰岛素抵抗的机制之一。血管张力和重塑由内皮细胞响应于包括高血压在内的多种血管损伤刺激而产生的多种血管活性自分泌/旁分泌因子控制。在培养的内皮细胞中检测到PPAR γ基因转录本. TZD的给药刺激了内皮细胞分泌C型利钠肽，C型利钠肽是利钠肽家族的一员，我们证明它是一种新的内皮源性舒张肽。同时，TZD显著抑制内皮素的分泌，内皮素是一种有效的内皮源性血管收缩肽。噻唑烷二酮类药物可通过调节内皮源性血管活性物质的产生，影响血管张力和生长，从而影响高血压和动脉粥样硬化的发生和发展。
1. Insulin resistance has been highlighted as a common causal factor for hypertension, hyperlipidaemia, diabetes mellitus and obesity, all of which are recognized to occur simultaneously; and a distinct clinical entity is defined as 'multiple risk factor syndrome'.2. Recently, a new class of antidiabetic agents, thiazolidinediones (TZD) has been developed and has been shown to improve insulin resistance by binding and activating a nuclear receptor, peroxisome proliferator-activated receptor (PPAR)gamma.3. cDNA of rat PPAR gamma 1 and gamma 2 were cloned and gene regulation of PPAR gamma in rat mature adipocytes was examined, Hydrogen peroxide, an oxygen radical, which is recognized to be the common intracellular signal for multiple risk factors, potently down-regulated PPAR gamma mRNA expression in rat mature adipocytes.4. Tumour necrosis factor (TNF)-alpha, which is considered to play a role in obesity-induced non-insulin-dependent diabetes mellitus and to augment oxidative stress, also suppressed PPAR gamma expression5. Thiazolidinediones dose-dependently recovered TNF-alpha-induced down-regulation of PPAR gamma mRNA expression,6. The modulation of PPAR gamma expression by TZD can he one mechanism for the improvement of insulin resistance by TZD,7. Vascular tone and remodelling are controlled by several vasoactive autocrine/paracrine factors produced by endothelial cells in response to several vascular injury stimuli, including hypertension. The PPAR gamma gene transcript was detected in cultured endothelial cells.8. The administration of TZD stimulated the endothelial secretion of type-C natriuretic peptide, which is one of the natriuretic peptide family and is demonstrated by us to act as a novel endothelium-derived relaxing peptide.9. Concomitantly, TZD significantly suppressed the secretion of endothelin, a potent endothelium-derived vasoconstricting peptide.10. Thiazolidinediones can affect vascular tone and growth by modulating the production of endothelium derived vasoactive substances to influence occurrence and progression of hypertension and atherosclerosis.