Yorek M A, Wiese T J, Davidson E P, Dunlap J A, Stefani M R, Conner C E, Lattimer S A, Kamijo M, Greene D A, Sima A A
Department of Internal Medicine, University of Iowa, Iowa City.
Diabetes. 1993 Oct;42(10):1401-6. doi: 10.2337/diab.42.10.1401.
L-Fucose is a monosaccharide that occurs in low concentrations in normal serum but has been shown to be increased in diabetic individuals. In cultured mammalian cells, L-fucose is a potent competitive inhibitor of myo-inositol transport. Abnormal myo-inositol metabolism has been proposed to be a factor in the development of diabetic complications. To test the hypothesis that myo-inositol deficiency may be responsible for the electrophysiological and biological defects in diabetic neuropathy, rats were fed a diet containing 10 or 20% L-fucose for a period of 6 wk. After 3 wk, the L-fucose diets in two groups of rats were supplemented with 1% myo-inositol. At the end of the study protocol, motor nerve conduction velocity, sciatic nerve tissue Na(+)-K(+)-ATPase activity, and myo-inositol content were determined. These results were compared with those of STZ-induced diabetic rats fed either a normal diet or a diet containing 1% myo-inositol or with those given 450 mg/kg body wt of sorbinil. Serum L-fucose levels were significantly increased in rats fed a diet containing 10 or 20% L-fucose. In comparison, the serum L-fucose levels in the diabetic rats were increased to a lesser extent. Motor nerve conduction velocity was significantly slower in rats fed a 10 or 20% L-fucose diet. Sciatic nerve composite and ouabain-sensitive Na(+)-K(+)-ATPase activity and myo-inositol content was also significantly decreased. Supplementation of 1% myo-inositol to the L-fucose-containing diet restored nerve myo-inositol levels and significantly improved Na(+)-K(+)-ATPase activity and motor nerve conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)
L-岩藻糖是一种单糖,在正常血清中含量较低,但在糖尿病患者中含量会升高。在培养的哺乳动物细胞中,L-岩藻糖是肌醇转运的有效竞争性抑制剂。异常的肌醇代谢被认为是糖尿病并发症发生发展的一个因素。为了验证肌醇缺乏可能是糖尿病神经病变电生理和生物学缺陷原因的假说,给大鼠喂食含10%或20% L-岩藻糖的饲料,持续6周。3周后,两组大鼠的L-岩藻糖饲料中添加1%的肌醇。在研究方案结束时,测定运动神经传导速度、坐骨神经组织钠钾ATP酶活性和肌醇含量。将这些结果与喂食正常饲料、含1%肌醇的饲料或给予450mg/kg体重索比尼尔的链脲佐菌素诱导的糖尿病大鼠的结果进行比较。喂食含10%或20% L-岩藻糖饲料的大鼠血清L-岩藻糖水平显著升高。相比之下,糖尿病大鼠的血清L-岩藻糖水平升高幅度较小。喂食10%或20% L-岩藻糖饲料的大鼠运动神经传导速度明显减慢。坐骨神经复合和哇巴因敏感的钠钾ATP酶活性以及肌醇含量也显著降低。在含L-岩藻糖的饲料中添加1%的肌醇可恢复神经肌醇水平,并显著改善钠钾ATP酶活性和运动神经传导速度。(摘要截短至250字)