Skip to Main content Skip to Navigation
Journal articles

Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal β-cell lines

Abstract : Insulin secretion from pancreatic ß-cells is controlled by complex metabolic and energetic changes provoked by exposure to metabolic fuels. Perturbations in these processes lead to impaired insulin secretion, the ultimate cause of Type 2 Diabetes. To increase our understanding of stimulus-secretion coupling and metabolic processes potentially involved in the pathogenesis of Type 2 Diabetes, a comprehensive investigation of the metabolic response in the glucose-responsive INS-1 832/13 and glucose-unresponsive INS-1 832/2 β-cell lines was performed. For this metabolomics analysis, we used gas chromatography/mass spectrometry combined with multivariate statistics. We found that perturbed secretion in the 832/2 line was characterized by disturbed coupling of glycolytic and TCA-cycle metabolism. The importance of this metabolic coupling was reinforced by our observation that insulin secretion partially could be reinstated by stimulation of the cells with mitochondrial fuels which bypass glycolytic metabolism. Furthermore, metabolic and functional profiling of additional ß-cell lines (INS-1, INS-1 832/1) confirmed the important role of coupled glycolytic and TCA-cycle metabolism in stimulus-secretion coupling. Dependence of the unresponsive clones on glycolytic metabolism was paralleled by increased stabilization of hypoxia-induced factor 1a (HIF-1a). The relevance of a similar perturbation for human Type 2 Diabetes was suggested by increased expression of HIF-1a target genes in islets from Type 2 Diabetes patients.
Mots-clés : Life Sciences
Document type :
Journal articles
Complete list of metadata

Cited literature [11 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-00576981
Contributor : Hal Peer <>
Submitted on : Wednesday, March 16, 2011 - 2:51:43 AM
Last modification on : Wednesday, March 16, 2011 - 2:51:43 AM
Long-term archiving on: : Sunday, December 4, 2016 - 12:54:37 AM

File

PEER_stage2_10.1042%2FBJ201006...
Files produced by the author(s)

Identifiers

Collections

Citation

Peter Spégel, Siri Malmgren, Vladimir V. Sharoyko, Philip Newsholme, Thomas Koeck, et al.. Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal β-cell lines. Biochemical Journal, Portland Press, 2011, 435 (1), pp.277-284. ⟨10.1042/BJ20100655⟩. ⟨hal-00576981⟩

Share

Metrics

Record views

129

Files downloads

367