Document Detail


Insulin detemir is not transported across the blood-brain barrier.
MedLine Citation:
PMID:  20868713     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin detemir has a different profile of action on the central nervous system (CNS) than human insulin. It has been hypothesized that this is caused by an altered ability of insulin detemir to cross the blood-brain barrier (BBB). Here, we measured the permeability of the BBB to insulin detemir. We labeled insulin detemir with radioactive iodine (I-Det) and examined its ability to cross the BBB of the mouse. Permeation was assessed after intravenous injection and by brain perfusion in the presence or absence of excess insulin detemir. The ability of insulin detemir to inhibit human insulin transport across the BBB was also assessed. I-Det did not cross the BBB either after intravenous injection or when studied by brain perfusion, a method which removes or reduces the influence of circulating proteins. Unlabeled detemir was about 10 times less potent than human insulin at inhibiting the transport of radioactive human insulin across the BBB. The altered CNS profile of insulin detemir may be caused by its poor access to CNS receptors and by a block of human insulin from crossing the BBB.
Authors:
William A Banks; John E Morley; Jessica L Lynch; Kristin M Lynch; Arshag D Mooradian
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Publication Detail:
Type:  Journal Article     Date:  2010-09-22
Journal Detail:
Title:  Peptides     Volume:  31     ISSN:  1873-5169     ISO Abbreviation:  Peptides     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2011-02-10     Revised Date:  2012-01-11    
Medline Journal Info:
Nlm Unique ID:  8008690     Medline TA:  Peptides     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2284-8     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
Affiliation:
GRECC, Veterans Affairs Puget Sound Health Care System, United States. wabanks1@u.washington.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport / physiology*
Blood-Brain Barrier / metabolism*
Brain / metabolism
Insulin / analogs & derivatives*,  pharmacokinetics
Insulin, Long-Acting
Male
Mice
Mice, Inbred ICR
Grant Support
ID/Acronym/Agency:
R01 AG029839-02/AG/NIA NIH HHS; R01 AG029839-05/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Insulin; 0/Insulin, Long-Acting; 0/insulin detemir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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