Obrenovich Mark E, Monnier Vincent M
Department of Pathology at Case Western Reserve University, Cleveland, OH 44106, USA.
Sci Aging Knowledge Environ. 2003 Mar 12;2003(10):PE6. doi: 10.1126/sageke.2003.10.pe6.
Diabetes accelerates the aging process and leads to complications that include blindness, renal failure, nerve damage, stroke, and cardiovascular disease. It has been hypothesized that high plasma glucose concentrations are responsible for increased mitochondrial free radical production and subsequent inactivation of glyceraldehyde phosphate dehydrogenase (GAPDH) in vascular endothelial cells and other cells implicated in these complications. As a result of the decreased ability of GAPDH to process upstream metabolites, three pathways of metabolic damage are activated, which include the advanced glycation end-product formation pathway, the protein kinase C pathway, and the hexosamine pathway. All three pathways have been implicated in abnormal cell signaling in diabetes. A group of German and U.S. scientists has now found that treating diabetic rats with high doses of benfotiamine, a lipid-soluble form of vitamin B1, can prevent diabetic retinopathy and all three forms of metabolic damage by stimulating transketolase activity and thus diverting excess metabolites toward the pentose pathway. Although vitamin B1 is available over the counter, the researchers at this time do not advocate self-treatment without further clinical data.
糖尿病会加速衰老进程，并引发包括失明、肾衰竭、神经损伤、中风和心血管疾病在内的并发症。据推测，高血浆葡萄糖浓度会导致线粒体自由基生成增加，进而使血管内皮细胞和与这些并发症相关的其他细胞中的甘油醛 - 3 - 磷酸脱氢酶（GAPDH）失活。由于GAPDH处理上游代谢物的能力下降，三种代谢损伤途径被激活，包括晚期糖基化终产物形成途径、蛋白激酶C途径和己糖胺途径。这三种途径都与糖尿病中的异常细胞信号传导有关。一组德国和美国科学家现已发现，用高剂量的苯磷硫胺（一种脂溶性维生素B1形式）治疗糖尿病大鼠，可以通过刺激转酮醇酶活性，从而将过量代谢物导向戊糖途径，预防糖尿病视网膜病变和所有三种形式的代谢损伤。虽然维生素B1可以非处方获得，但研究人员目前不主张在没有进一步临床数据的情况下自行治疗。
