Linked Life Data

11440359

Source:http://linkedlifedata.com/resource/pubmed/id/11440359

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-7-6
pubmed:abstractText
Protein kinase C (PKC) is a family of multifunctional isoenzymes, activated by diacylglycerols (DAGs), which play a central role in signal transduction and intracellular crosstalk by phosphorylating at serine/threonine residues an array of substrates, including cell-surface receptors, enzymes, contractile proteins, transcription factors and other kinases. Individual isozymes vary in their pattern of tissue and subcellular distribution, function and Ca2+/phospholipid cofactor requirements, and in diabetes there is widespread activation of the DAG-PKC pathway in metabolic, cardiovascular and renal tissues. In liver, muscle and adipose tissue, PKC isozymes have been implicated both as mediators and inhibitors of insulin action. Activation of DAG-sensitive PKC isoforms, such as PKC-theta and PKC-epsilon, down-regulates insulin receptor signalling and could be an important biochemical mechanism linking dysregulated lipid metabolism and insulin resistance in muscle. On the other hand, atypical PKC isozymes, such as PKC-zeta and PKC-lambda, have been identified as downstream targets of PI-3-kinase involved in insulin-stimulated glucose uptake, especially in adipocytes. Glucose-induced de novo synthesis of (palmitate-rich) DAG and sustained isozyme-selective PKC activation (especially but not exclusively PKC-beta) has been strongly implicated in the pathogenesis of diabetic microangiopathy and macroangiopathy through a host of undesirable effects on endothelial function, VSM contractility and growth, angiogenesis, gene transcription (in part by MAP-kinase activation) and vascular permeability. Interventions that increase DAG metabolism (e. g. vitamin E) and/or inhibit PKC isozymes (e. g. the beta-selective inhibitor LY333531) ameliorate the biochemical and functional consequences of DAG-PKC activation in experimental diabetes, for example improving retinal blood flow and albuminuria in parallel with reductions in membrane-associated PKC isozyme activities. Thus, a greater understanding of the functional diversity and pathophysiological regulation of PKC isozymes is likely to have important clinical and therapeutic benefits.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0012-186X
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
659-73
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes.
pubmed:affiliation
School of Medical and Surgical Sciences, University of Nottingham, Royal Infirmary, Derby, UK.
pubmed:publicationType
Journal Article, Review