Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine
Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine
复制标题
DOI：
10.2337/diabetes.52.8.2110
复制
发表时间：
2003-08-01
期刊：
影响因子：
7.7
通讯作者：
Thornalley, PJ
中科院分区：
文献类型：
--
作者：
Babaei-Jadidi, R;Karachalias, N;Thornalley, PJ
高血糖时由高胞内葡萄糖浓度引起的三磷酸酯积累是生化功能障碍的触发因素，导致糖尿病肾病的发展——糖尿病的常见并发症，与心血管疾病和死亡率的高风险相关。在这里，我们报道了通过高剂量硫胺素和硫胺素单磷酸衍生物苯福地胺治疗刺激还原性戊磷酸酯途径，可以对抗实验性糖尿病中三磷酸的积累，并抑制早期肾病的发展。高剂量硫胺素和苯福地胺治疗增加肾小球转酮醇酶的表达，增加三磷酸酯向5-磷酸核糖的转化，并强烈抑制微量白蛋白尿的发生。这与蛋白激酶C激活降低、蛋白糖化和氧化应激降低有关，这是高血糖中生化功能障碍的三个主要途径。苯福胺还能抑制糖尿病引起的高滤过。在糖尿病状态下，血糖浓度升高和糖化血红蛋白没有改变。大剂量硫胺素联合苯福地胺治疗是一种潜在的预防糖尿病肾病的新策略。
Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy. High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. This was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change In elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.