Kondo Y, Nakatani A, Hayashi K, Ito M
Laboratory of Analytical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Biol Pharm Bull. 2000 Dec;23(12):1458-64. doi: 10.1248/bpb.23.1458.
The present study was designed to clarify the effect of low molecular weight (LMW) chitosan (chitosan lactate, average MW: 20000) on the progression of slowly progressive non-insulin-dependent diabetes mellitus (NIDDM) induced by a single i.p. injection of low dose (100 mg/kg) streptozotocin (STZ) to 8-week-old male ICR mice. The non-fasting serum glucose levels of STZ-treated control mice continued to rise throughout the experimental period until 23 weeks after STZ treatment. The 0.2% or 0.8% chitosan (water solution), given as drinking water from prediabetic stage (2 weeks after STZ treatment), markedly prevented the time course-related rise of serum glucose levels of diabetic mice. In addition, the reduction of relative numbers of insulin-immunoreactive cells (beta-cells) in the islets of diabetic mice at 24 weeks after STZ treatment was markedly prevented by 0.2% or 0.8% chitosan administration. However, the progression of hyperglycemia in diabetic mice was not affected by 0.2% glucosamine, a monosaccharide of chitosan. The glucose levels of normal mice were not affected by 0.8% chitosan administration. When 0.2% chitosan administration was stopped at 20 weeks, these animals had still maintained significantly lower serum glucose levels, compared to control animals, even at 5 weeks after stopping the administration. These results indicate that LMW chitosan prevents the progression of low dose STZ-induced slowly progressive NIDDM.
本研究旨在阐明低分子量(LMW)壳聚糖(乳酸壳聚糖,平均分子量:20000)对8周龄雄性ICR小鼠单次腹腔注射低剂量(100mg/kg)链脲佐菌素(STZ)诱导的缓慢进展性非胰岛素依赖型糖尿病(NIDDM)进展的影响。STZ处理的对照小鼠的非空腹血清葡萄糖水平在整个实验期内持续升高,直至STZ处理后23周。从糖尿病前期阶段(STZ处理后2周)开始以饮用水形式给予0.2%或0.8%壳聚糖(水溶液),可显著阻止糖尿病小鼠血清葡萄糖水平随时间的升高。此外,在STZ处理后24周时,给予0.2%或0.8%壳聚糖可显著阻止糖尿病小鼠胰岛中胰岛素免疫反应性细胞(β细胞)相对数量的减少。然而,糖尿病小鼠高血糖的进展不受壳聚糖单糖0.2%氨基葡萄糖的影响。给予0.8%壳聚糖对正常小鼠的血糖水平没有影响。当在20周时停止给予0.2%壳聚糖时,即使在停止给药5周后,与对照动物相比,这些动物的血清葡萄糖水平仍显著较低。这些结果表明,低分子量壳聚糖可阻止低剂量STZ诱导的缓慢进展性NIDDM的进展。