Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines
Insulin secretion from pancreatic β-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 T2D (Type 2 diabetes). To increase our understanding of stimulus–secr...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
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Portland Press Ltd.
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/29460 |
| _version_ | 1848752809687646208 |
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| author | Spegel, P. Malmgren, S. Newsholme, Philip Koeck, T. Mulder, H. Sharoyko, V. |
| author_facet | Spegel, P. Malmgren, S. Newsholme, Philip Koeck, T. Mulder, H. Sharoyko, V. |
| author_sort | Spegel, P. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Insulin secretion from pancreatic β-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 T2D (Type 2 diabetes). To increase our understanding of stimulus–secretion coupling and metabolic processes potentially involved in the pathogenesis of T2D, 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 GC/MS (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 (tricarboxylic acid)-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 β-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 HIF-1α (hypoxia-inducible factor 1α). The relevance of a similar perturbation for human T2D was suggested by increased expression of HIF-1α target genes in islets from T2D patients. |
| first_indexed | 2025-11-14T08:14:31Z |
| format | Journal Article |
| id | curtin-20.500.11937-29460 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:14:31Z |
| publishDate | 2011 |
| publisher | Portland Press Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-294602023-02-22T06:24:18Z Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines Spegel, P. Malmgren, S. Newsholme, Philip Koeck, T. Mulder, H. Sharoyko, V. Type 2 diabetes (T2D) mitochondria pancreatic islet insulin hypoxia-inducible factor (HIF) Insulin secretion from pancreatic β-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 T2D (Type 2 diabetes). To increase our understanding of stimulus–secretion coupling and metabolic processes potentially involved in the pathogenesis of T2D, 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 GC/MS (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 (tricarboxylic acid)-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 β-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 HIF-1α (hypoxia-inducible factor 1α). The relevance of a similar perturbation for human T2D was suggested by increased expression of HIF-1α target genes in islets from T2D patients. 2011 Journal Article http://hdl.handle.net/20.500.11937/29460 10.1042/BJ20100655 Portland Press Ltd. unknown |
| spellingShingle | Type 2 diabetes (T2D) mitochondria pancreatic islet insulin hypoxia-inducible factor (HIF) Spegel, P. Malmgren, S. Newsholme, Philip Koeck, T. Mulder, H. Sharoyko, V. Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines |
| title | Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines |
| title_full | Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines |
| title_fullStr | Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines |
| title_full_unstemmed | Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines |
| title_short | Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines |
| title_sort | metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal ß-cell lines |
| topic | Type 2 diabetes (T2D) mitochondria pancreatic islet insulin hypoxia-inducible factor (HIF) |
| url | http://hdl.handle.net/20.500.11937/29460 |