Hayashi M, Shimosawa T, Fujita T
School of Medicine, University of Tokyo, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo, 112-8688, Japan.
Biochem Biophys Res Commun. 1999 May 10;258(2):453-6. doi: 10.1006/bbrc.1999.0664.
We have reported that plasma adrenomedullin (AM) in hyperglycemic patients was significantly increased compared with normal volunteers. In this report we examined the effects of hyperglycemia on AM expression in the vasculature, the main site of AM production. AM mRNA level in the aorta was higher in the diabetic rats than in the control rats. AM mRNA level and protein kinase C (PKC) activity in cultured vascular smooth muscle cells (VSMC) increased as the glucose concentration in the medium changed from 100mg/dl to 450mg/dl. PKC inhibitors blocked this increase of AM mRNA. Similar osmotic change with mannitol had no effect on AM expression. We conclude that (1) hyperglycemia increases vascular AM expression through PKC-dependent pathway, and (2) the elevated plasma AM in hyperglycemic patients originates from the glucose induced vascular AM expression. We propose the possible role of AM in the pathogenesis of diabetic vascular complications.
我们曾报道，与正常志愿者相比，高血糖患者血浆中的肾上腺髓质素（AM）显著升高。在本报告中，我们研究了高血糖对血管（AM产生的主要部位）中AM表达的影响。糖尿病大鼠主动脉中的AM mRNA水平高于对照大鼠。当培养基中的葡萄糖浓度从100mg/dl变为450mg/dl时，培养的血管平滑肌细胞（VSMC）中的AM mRNA水平和蛋白激酶C（PKC）活性增加。PKC抑制剂可阻断AM mRNA的这种增加。用甘露醇进行的类似渗透变化对AM表达没有影响。我们得出结论：（1）高血糖通过PKC依赖性途径增加血管AM表达，并且（2）高血糖患者血浆AM升高源自葡萄糖诱导的血管AM表达。我们提出了AM在糖尿病血管并发症发病机制中的可能作用。
