Document Detail

Time-resolved metabolomics analysis of ß-cells implicates the pentose phosphate pathway in the control of insulin release.
MedLine Citation:
PMID:  23282133     Owner:  NLM     Status:  Publisher    
Insulin secretion is coupled to changes in ß-cell metabolism. To define this process, 195 putative metabolites, mitochondrial respiration, NADP+, NADPH, and insulin secretion were measured within 15 minutes after stimulation of clonal INS-1 832/13 ß-cells with glucose. Rapid responses in the major metabolic pathways of glucose occurred, involving several previously suggested metabolic coupling factors. The complexity of metabolite changes observed disagreed with the concept of one single metabolite controlling insulin secretion. The complex alterations in metabolite levels suggest that a coupling signal should reflect large parts of the ß-cell metabolic response. This was fulfilled by the NADPH/NADP+-ratio, which was elevated (8-fold, p<0.01) at 6 min after glucose stimulation. The NADPH/NADP+-ratio paralleled an increase in ribose-5-phosphate (+2.5-fold; p<0.001). Inhibition of the pentose phosphate pathway by trans-dehydroepiandrosterone suppressed ribose-5-phosphate levels and production of reduced glutathione, as well as insulin secretion in INS-1 832/13 ß-cells and rat islets without affecting ATP production. Metabolite profiling of rat islets confirmed the glucose-induced rise in ribose-5-phosphate, which was prevented by trans-dehydroepiandrosterone. These findings implicate the pentose phosphate pathway, and support a role for NADPH and glutathione, in ß-cell stimulus-secretion coupling.
Peter Spégel; Vladimir V Sharoyko; Isabel Göhring; Anders P H Danielsson; Siri Malmgren; Cecilia L F Nagorny; Lotta E Andersson; Thomas Koeck; Geoffrey W G Sharp; Susanne G Straub; Claes B Wollheim; Hindrik Mulder
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-2
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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