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Time-resolved metabolomics analysis of β-cells implicates the pentose phosphate pathway in the control of insulin release

Spégel, Peter
Sharoyko, Vladimir V
Goehring, Isabel
Danielsson, Anders P H
Malmgren, Siri
Nagorny, Cecilia L F
Andersson, Lotta E
Koeck, Thomas
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Published in Biochemical journal. 2013, vol. 450, no. 3, p. 595-605
Abstract Insulin secretion is coupled with changes in β-cell metabolism. To define this process, 195 putative metabolites, mitochondrial respiration, NADP+, NADPH and insulin secretion were measured within 15 min of stimulation of clonal INS-1 832/13 β-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 β-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 (DHEA) suppressed ribose 5-phosphate levels and production of reduced glutathione, as well as insulin secretion in INS-1 832/13 β-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 DHEA. These findings implicate the pentose phosphate pathway, and support a role for NADPH and glutathione, in β-cell stimulus-secretion coupling.
Keywords AnimalsCell Respiration/physiologyCells, CulturedGlucose/pharmacologyInsulin/secretionInsulin-Secreting Cells/chemistry/metabolism/secretionIslets of Langerhans/metabolism/secretionMaleMetabolomeMetabolomics/methodsMitochondria/metabolism/physiologyPentose Phosphate Pathway/drug effects/physiologyRatsRats, WistarSecretory Pathway/drug effects
PMID: 23282133
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SPÉGEL, Peter et al. Time-resolved metabolomics analysis of β-cells implicates the pentose phosphate pathway in the control of insulin release. In: Biochemical journal, 2013, vol. 450, n° 3, p. 595-605. doi: 10.1042/BJ20121349 https://archive-ouverte.unige.ch/unige:33559

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Deposited on : 2014-01-22

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