Linked Life Data

1294187

Source:http://linkedlifedata.com/resource/pubmed/id/1294187

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1993-4-12
pubmed:abstractText
During storage of insulin formulated for therapy, minor amounts of various degradation and covalent di- and polymerization products are formed [1-3]. The main chemical transformation products were isolated from aged preparations and characterized chemically and biologically. The most prominent products formed in neutral medium were identified as a mixture of deamidation products hydrolyzed at residue B3, namely isoAsp B3 and Asp B3 derivatives. A hydrolysis product formed only in crystals of insulin zinc suspensions containing a surplus of zinc ions in the supernatant was identified as an A8-A9 cleavage product. The small amounts of covalent insulin dimers (CID) formed in all formulations were shown to be a heterogenous mixture of 5-6 different CIDs with a composition dependent on the pharmaceutical formulation. The chemical characteristics of the CIDs indicate that they are formed through a transamidation reaction mainly between the B-chain N-terminal and one of the four amide side-chains of the A chain. GlnA15, AsnA18 and, in particular, AsnA21 participate in the formation of such isopeptide links between two insulin molecules. The covalent insulin-protamine products (CIPP) formed during storage of NPH preparations presumably originate from a similar reaction between the protamine N-terminal with an amide in insulin. Covalent polymerization products, mainly formed during storage of amorphously suspended insulin at higher temperature, were shown to be due to disulfide interactions. Biological in vivo potencies relative to native insulin were less than 2% for the split-(A8-A9)-product and for the covalent disulfide exchange polymers, 4% for the CIPP, approximately 15% for the CIDs, whereas the B3 derivatives exhibited full potency. Rabbit immunization experiments revealed that none of the insulin transformation products had significantly increased immunogenicity in rabbits.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1100-1801
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
223-32
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Chemical stability of insulin. 5. Isolation, characterization and identification of insulin transformation products.
pubmed:affiliation
Novo Research Institute, Bagsvaerd, Denmark.
pubmed:publicationType
Journal Article