Low molecular weight chitosan prevents the progression of low dose streptozotocin-induced slowly progressive diabetes mellitus in mice.
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.
Kondo
Y
Y
Laboratory of Analytical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Nakatani
A
A
Hayashi
K
K
Ito
M
M
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002686:Chitin / Q000031:analogs & derivatives / Q000494:pharmacology*; D048271:Chitosan; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000209:etiology
D001786:Blood Glucose; D002686:Chitin; D019344:Lactic Acid; D048271:Chitosan; D005944:Glucosamine