Document Detail

Islet blood flow in multiple low dose streptozotocin-treated wild-type and inducible nitric oxide synthase-deficient mice.
MedLine Citation:
PMID:  10919259     Owner:  NLM     Status:  MEDLINE    
The present study tested the hypothesis that changes in islet blood perfusion occur during the development of diabetes in the multiple low dose streptozotocin-treated mouse. Streptozotocin (40 mg/kg) or citrate buffer was given ip once daily for 5 consecutive days to wild-type and inducible nitric oxide synthase (iNOS)-deficient C57BL/6 x 129 SvEv hybrid mice. The blood flows were then determined by a microsphere technique. The islet blood perfusion was almost 2-fold higher in wild-type mice treated with streptozotocin than in those given vehicle. Whole pancreatic blood flow was also increased in the streptozotocin-treated wild-type mice. In iNOS-deficient mice, neither islet blood flow nor whole pancreatic blood flow was affected by repeated streptozotocin treatment. These combined findings suggest an increased islet blood perfusion in the prediabetic stage mediated by an iNOS-dependent mechanism. In combination with increased vasopermeability and expression of adhesion molecules on the islet endothelium, as previously described, this increased islet blood flow may be of crucial importance for the recruitment of inflammatory cells into the islets during the development of diabetes in this animal model. Indeed, an increased degree of insulitis was observed in wild-type mice compared with mice deficient in iNOS as well as a more rapid decrease in islet volume and an earlier debut of manifest diabetes. We also describe altered islet blood perfusion in the iNOS-deficient mice during basal conditions due to a compensatory increase in constitutive NOS activity.
P O Carlsson; M Flodström; S Sandler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  141     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-08-16     Completed Date:  2000-08-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2752-7     Citation Subset:  AIM; IM    
Department of Medical Cell Biology, Uppsala University, Sweden.
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MeSH Terms
Blood Glucose / metabolism
Colon / blood supply
Diabetes Mellitus, Experimental / physiopathology*
Duodenum / blood supply
Ileum / blood supply
Islets of Langerhans / blood supply*,  drug effects
Mice, Inbred C57BL
Nitric Oxide Synthase / deficiency*
Nitric Oxide Synthase Type II
Pancreas / blood supply,  drug effects
Streptozocin / administration & dosage*
Reg. No./Substance:
0/Blood Glucose; 18883-66-4/Streptozocin; EC Oxide Synthase; EC Oxide Synthase Type II; EC protein, mouse

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