Protection against hyperglycemia in female nonobese diabetic mice treated with 15-deoxyspergualin.
The effects of 15-deoxyspergualin (15-DS), a newly described immunosuppressive agent, have been studied on the development of diabetes in female NOD mice. 15-DS treatment was started two weeks after weaning i.e. at five weeks of age. The mice received either one daily intraperitoneal injection of 15-DS (2.5 mg/kg body weight) or saline for two weeks. The mice were then injected every third day up to eight months of age for evaluation of the diabetes incidence. In another set of experiments the mice were treated up to three months of age, whereafter islet insulin release, islet insulin content and DNA content was measured together with an evaluation of spleen cell proliferation rates. Different spleen cell subsets were studied directly after the two weeks of daily injections. In the saline group 8 out of 9 mice developed diabetes, whereas only 4 out of 11 of the 15-DS treated mice became diabetic (p < 0.05). There was no difference between the groups in islet insulin release in response to glucose, however, the islet insulin release increased after one week in culture. The 15-DS treatment did not affect the insulin or DNA content of the isolated islets or the insulin concentration in the pancreas. No detectable changes in the relative number of CD4+ and CD8+ T-cell subsets in the spleen were seen and there were no obvious differences in splenocyte proliferation rates. The histological examinations of the pancreatic glands showed gradual increasing signs of islet inflammation with age and 15-DS could apparently not prevent this.(ABSTRACT TRUNCATED AT 250 WORDS)
Strandell
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Department of Medical Cell Biology, Uppsala University, Sweden.
Sandler
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D000367:Age Factors; D000818:Animals; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000633:toxicity; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000473:pathology
D006146:Guanidines; D007166:Immunosuppressive Agents; D007328:Insulin; D003520:Cyclophosphamide; C037258:gusperimus