Altered intracellular signalling in response to hyperglycaemia reflects an inherent predisposition to nephropathy

高血糖引起的细胞内信号传导改变反映了肾病的固有倾向

• 批准号: nhmrc : 107410
• 负责人: Prof Carol Pollock
• 金额: $ 10.94万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/altered-intracellular-signalling-predisposition-nephropathy/96917
• 关键词: Altered; intracellular; signalling; response; hyperglycaemia

Diabetic nephropathy affects 30-50% of patients with diabetes mellitus. The reasons as to why only a proportion of patients develop this devastating complication is not clear. Poor control of blood sugar levels has been well characterised as being of aetiological importance in its genesis, but is clearly not the sole factor responsible. Genetic factors appear to predispose individuals to developing diabetic nephropathy, with a significantly higher number of affected patients having a family history of hypertension and vascular disease. Our own preliminary studies using cells from human kidneys have demonstrated that there are clearly 2 responses observed with respect to alterations in intracellular signalling after exposure to high glucose concentrations and hormones known to be of importance in the development of diabetic nephropathy (such as angiotensin II and insulin-like growth factor-1). These responses appear to be specific to the patient from which the kidney tissue is derived. Thus the aim of the present study is to determine prospectively, whether the groups differ with regards their intracellular signalling and subsequent development of tubulointerstitial pathology in an in vitro model of diabetes mellitus.

糖尿病肾病影响 30-50% 的糖尿病患者。为什么只有一部分患者出现这种破坏性并发症的原因尚不清楚。血糖水平控制不良在其发生过程中具有重要的病因学特征，但显然不是唯一的原因。遗传因素似乎使个体容易患上糖尿病肾病，有高血压和血管疾病家族史的患者数量显着增加。我们自己使用人类肾脏细胞进行的初步研究表明，在暴露于高浓度葡萄糖和已知对糖尿病肾病发展至关重要的激素（例如血管紧张素 II 和胰岛素样生长因子-1）后，明显观察到细胞内信号传导发生两种反应。这些反应似乎是肾组织来源患者所特有的。因此，本研究的目的是前瞻性地确定各组在糖尿病体外模型中的细胞内信号传导和肾小管间质病理学的后续发展方面是否存在差异。