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

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会出现这种毁灭性的并发症，原因尚不清楚。对血糖水平的不良控制一直被很好地描述为其病因学上的重要性，但显然不是唯一的原因。遗传因素似乎容易使个人患上糖尿病肾病，有高血压和血管疾病家族史的受影响患者的数量明显更高。我们自己使用人类肾脏细胞进行的初步研究表明，在暴露于高葡萄糖浓度和已知在糖尿病肾病发展中起重要作用的激素(如血管紧张素II和胰岛素样生长因子-1)后，细胞内信号的变化明显有两种反应。这些反应似乎对肾组织来源的患者是特异的。因此，本研究的目的是在体外糖尿病模型中，前瞻性地确定这两组患者在细胞内信号和随后发生的肾小管间质病变方面是否存在差异。

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.