Cyclophosphamide-induced diabetes in Long-Evans Tokushima Lean rats: influence of ovariectomy on the development of diabetes.
We studied the effect of treatment with cyclophosphamide (CY) on the incidence of diabetes in Long-Evans Tokushima Lean (LETL) rats, a newly established strain of spontaneously type I diabetic rats. The overall incidence of diabetes among 356 LETL rats treated with CY was 25.6%, which was significantly higher than the 10.5% among 857 untreated LETL rats at 27 weeks of age, and there was no significant sex difference. The incidence of CY-induced diabetes in adult (> 16 weeks of age) female LETL rats was 7.7% (10/130), which was significantly lower than that in other CY-treated groups of LETL rats. No diabetes mellitus was induced by administration of CY to 23 diabetes-resistant LETO rats. There were no significant differences in the degrees of hyperglycemia or hyperketonemia in spontaneously and CY-induced diabetic LETL rats, but the plasma glycated albumin level of CY-induced diabetic rats (10.3% +/- 2.1%) was significantly higher than that of spontaneously diabetic rats (8.2% +/- 1.3%), suggesting that plasma glucose levels increased more rapidly in the latter. More than half of the diabetic rats showed type C or D morphological changes of the islets, ie, atrophic change with little mononuclear cell infiltration or almost complete loss of the islets. However, distributions of various types of morphological changes in the islets were not significantly different in the two groups. Ovariectomy (OVX) significantly increased the incidence of CY-induced diabetes in adult female rats from 7.7% to 20.8%. The number of CD8+ cells was significantly increased in noncastrated adult female LETL rats and decreased to the level of other groups after OVX.(ABSTRACT TRUNCATED AT 250 WORDS)
Mizuno
A
A
Department of Laboratory Medicine, School of Medicine, University of Tokushima, Japan.
Iwami
T
T
Sano
T
T
Shi
K
K
Noma
Y
Y
Shima
K
K
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D005260:Female; D016131:Lymphocyte Subsets; D008297:Male; D010052:Ovariectomy; D051381:Rats
D003520:Cyclophosphamide