Red blood cells sorbitol as a mark for detecting T2DM neuropathy

• Main Authors: Shu-Fen Chen, 陳淑芬
• Other Authors: Ching-Feng Weng
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/kyh2qg

碩士 === 國立東華大學 === 生物技術研究所 === 96 === Numerous chronic side effects are caused by diabetes, such as peripheral neuropathy. In nerves, the accumulation of excess glucose may activate the polyol pathway to induce the accumulation of sorbitol and consequently triggers neuropathy. Excess glucose is catalyzed by aldose reductase and produces large amount sorbitol during the metabolic process of polyol pathway. The elevation of polyol pathway activity is further depleted myo-inositol. This myo-inositol depletion is accompanied by an interference of phosphatidyl inositol turnover that is thought to impair Na+/K+ ATPase activity. This impairment Na+/K+ ATPase activity leads to an increase in the intracellular concentration of sodium and decrease the nerve function. Additionally, the accumulation of sorbitol in red blood cell (RBC) is activated by hyperglycemia through polyol pathway. The aim of the present study was to measure the accumulated amount of sorbitol in RBC and sciatic nerve using diabetic rats and to evaluate whether RBC sorbitol can be used as a diagnostic marker for the early stage of diabetic peripheral neuropathy. In this study, high fat fed rats were administrated with 30 mg/kg streptozotocin (i.p) to induce type II diabetes (T2DM). The results showed that T2DM rats had the symptoms of high blood glucose level, insulin resistance, polyphagia, polydipsia and polyuria. The measurements of glucose, sorbitol and myo-inositol using benzylation followed RP-HPLC, the results showed that the amount of sorbitol in RBC was found to be increased before 15th week and reached the plateau at 19th week. According to the amount of sorbitol in RBC and HbA1c in diabetic rats, the results found that hyperglycemia activated the polyol pathway and subsequently caused the accumulation of sorbitol in RBC. The amount of glucose, sorbitol and myo-inositol in sciatic nerve was determined in the 16th, 20th and 24th week; the data revealed that polyol pathway of sciatic nerve was activated in the presence of excess glucose environment, both glucose and sorbitol increased continuously. Sciatic nerve was damaged through the decreasing expression of Na+/K+-ATP α1 and ATF3. The accumulation of glucose in sciatic nerve further increased the expression of AR and SDH, and activated polyol pathway which sequentially caused the accumulation of sorbitol. Taken altogether, it is evident that the level of sorbitol in RBC can take as the diagnostic index of diabetic peripheral neuropathy during the initial stage.