Linked Life Data

12145163

Source:http://linkedlifedata.com/resource/pubmed/id/12145163

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-7-29
pubmed:abstractText
The secondary signals emanating from increased glucose metabolism, which lead to specific increases in proinsulin biosynthesis translation, remain elusive. It is known that signals for glucose-stimulated insulin secretion and proinsulin biosynthesis diverge downstream of glycolysis. Consequently, the mitochondrial products ATP, Krebs cycle intermediates, glutamate, and acetoacetate were investigated as candidate stimulus-coupling signals specific for glucose-induced proinsulin biosynthesis in rat islets. Decreasing ATP levels by oxidative phosphorylation inhibitors showed comparable effects on proinsulin biosynthesis and total protein synthesis. Although it is a cofactor, ATP is unlikely to be a metabolic stimulus-coupling signal specific for glucose-induced proinsulin biosynthesis. Neither glutamic acid methyl ester nor acetoacetic acid methyl ester showed a specific effect on glucose-stimulated proinsulin biosynthesis. Interestingly, among Krebs cycle intermediates, only succinic acid monomethyl ester specifically stimulated proinsulin biosynthesis. Malonic acid methyl ester, an inhibitor of succinate dehydrogenase, also specifically increased glucose-induced proinsulin biosynthesis without affecting islet ATP levels or insulin secretion. Glucose caused a 40% increase in islet intracellular succinate levels, but malonic acid methyl ester showed no further effect, probably due to efficient conversion of succinate to succinyl-CoA. In this regard, a GTP-dependent succinyl-CoA synthetase activity was found in cytosolic fractions of pancreatic islets. Thus, succinate and/or succinyl-CoA appear to be preferential metabolic stimulus-coupling factors for glucose-induced proinsulin biosynthesis translation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2496-504
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12145163-Adenosine Triphosphate, pubmed-meshheading:12145163-Animals, pubmed-meshheading:12145163-Calcium, pubmed-meshheading:12145163-Carboxylic Acids, pubmed-meshheading:12145163-Cell Fractionation, pubmed-meshheading:12145163-Fumarates, pubmed-meshheading:12145163-Glucose, pubmed-meshheading:12145163-Islets of Langerhans, pubmed-meshheading:12145163-Malates, pubmed-meshheading:12145163-Male, pubmed-meshheading:12145163-Oxidative Phosphorylation, pubmed-meshheading:12145163-Proinsulin, pubmed-meshheading:12145163-Protein Biosynthesis, pubmed-meshheading:12145163-Rats, pubmed-meshheading:12145163-Rats, Sprague-Dawley, pubmed-meshheading:12145163-Signal Transduction, pubmed-meshheading:12145163-Somatostatin, pubmed-meshheading:12145163-Substrate Specificity, pubmed-meshheading:12145163-Succinates
pubmed:year
2002
pubmed:articleTitle
Succinate is a preferential metabolic stimulus-coupling signal for glucose-induced proinsulin biosynthesis translation.
pubmed:affiliation
Pacific Northwest Research Institute, Seattle, Washington 98122, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't