Linked Life Data

19817801

Source:http://linkedlifedata.com/resource/pubmed/id/19817801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-10-12
pubmed:abstractText
The preeminent role of the beta cell is to manufacture, store and release insulin. The mature insulin molecule is composed of two polypeptide chains designated as A and B that are joined by two pairs of disulfide bonds with an additional intramolecular disulfide bond in the A chain. However, the two chains of the insulin molecule are not synthesized as separate polypeptide chains but rather are generated by specific proteolytic processing of a larger precursor, proinsulin. This discovery in 1967 and the concept of prohormones changed our view of the biosynthesis of hormones and neuropeptides. It allowed studies of the regulation of insulin biosynthesis that highlighted the key role of glucose. In addition, the C-peptide, the polypeptide that joins the A and B chains in proinsulin and is stored with insulin in the secretory granules and secreted in equimolar amounts, allowed studies of pancreatic beta cell function in vivo including in patients with diabetes. Subsequent studies have identified the specific proteases, prohormone convertases 1/3 and 2 and carboxypeptidase E, that are involved in the conversion of proinsulin to proinsulin intermediates and then to insulin. Disorders of (pro)insulin biosynthesis continue to illuminate important aspects of this pathway, revealing important connections to diabetes pathogenesis. Recent studies of patients with insulin gene mutations that cause permanent neonatal diabetes have identified key residues affecting the folding and structural organization of the preproinsulin molecule and its subsequent processing. These findings have renewed interest in the key role of endoplasmic reticulum function in insulin biosynthesis and the maintainance of normal beta cell health.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1463-1326
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
11 Suppl 4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
189-96
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A brief perspective on insulin production.
pubmed:affiliation
Department of Biochemistry, The University of Chicago, IL 60637, USA. dfsteine@uchicago.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't