Role of 3-deoxyglucosone in the pathogenesis of uremic and diabetic complications

3-脱氧葡萄糖（3-DG）是美拉德反应的活性中间体，美拉德反应是蛋白质的非酶糖基化反应。为了研究3-DG在尿毒症和糖尿病并发症发病机制中的作用，我们制备了一种抗AGE抗体（AG-1），该抗体可与新型晚期糖基化终产物（AGE）咪唑酮特异性反应。咪唑酮是精氨酸的胍基与3-DG的反应产物。我们证明了咪唑酮修饰了DRA患者的淀粉样组织beta_2m。此外，我们利用抗体免疫组化方法研究了咪唑酮在糖尿病患者肾脏和主动脉中的定位。在糖尿病肾病晚期肾小球结节性病变、肾小球系膜基质扩张、肾动脉及主动脉动脉粥样硬化性病变中检测特异性咪唑酮免疫反应性。这些结果，加上最近尿毒症和糖尿病患者血清3-DG水平升高的证据，强烈表明3-DG产生的咪唑酮可能有助于长期尿毒症和糖尿病并发症的进展，如透析相关淀粉样变性、糖尿病肾病和动脉粥样硬化。

3-Deoxyglucosone (3-DG) is a reactive intermediate of the Maillard reaction which is a nonenzymatic glycation reaction of proteins. To investigate the role of 3-DG in the pathogenesis of uremic and diabetic complications, we produced and anti-AGE antibody (AG-1) that reacted specifically with imidazolone, a novel advanced glycation end products (AGE). The imidazolone is the reaction products of the guanidino group of arginine with 3-DG.We demonstrated that amyloid tissue beta_2m is modified with imidazolone in patients with DRA.Further, we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody. Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in advanced stage of diabetic nephropathy as well as in atherosclerotic lesions of aortas. These results, taken together with a recent demonstration of increased serum 3-DG levels in uremia and diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term uremic and diabetic complications such as dialysis-related amyloidosis, and diabetic nephropathy and atherosclerosis.