The production of mouse model of slowly progressive diabetes mellitus and the preventive effect of low molecular weight chitosan on the progression of the diabetes mellitus

Abstract

The aim of our study was to produce a new diabetic model by a single i.p. injection of various doses of streptozoto-cin (STZ) to 8-week-old male Institute of Cancer Research (ICR) mice. When STZ was i.p. injected at doses rainging from 75 to 200 mg/kg, in the group injected 200 mg/kg STZ, the non-fasting serum glucose levels markedly rose from 1 week after STZ administration and the high glucose levels were maintained for 9 weeks. The serum glucose levels in the group administered 100 mg/kg STZ were within a normal range at 1 week after STZ administration, but thereafter continued to increase gradually till 9 weeks. In contrast with the serum glucose levels, a marked reduction in the percentage of the relative numbers of β-cells in the islets of pancreas from 1 week in mice injected 200 mg/kg STZ was observed. On the other hand, in 100 mg/kg STZ mice, the number of β-cells was almost normal percentage at 1 week and then continued to gradually decrease as the time went on throughout 24-week-observation. These results indicate that only the 100 mg/kg STZ injection produces slowly progressive diabetes mellitus in mice. Low molecular weight (LMW) chitosan (chitosan lactate, average of molecular weight: 20000) was administered as drinking water from prediabetic stage (from 2 weeks after 100 mg/kg STZ injection). The 0.2% or 0.8% LMW chitosan administration prevented the progression of 100 mg/kg STZ-induced slowly progressive diabetes mellitus. The mechanisms, which LMW chitosan is effective in this model may be discussed on β-cells. © 2013 The Pharmaceutical Society of Japan.