Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal beta-cell lines
Spégel, Peter LU ; Malmgren, Siri LU ; Sharoyko, Vladimir LU ; Newsholme, Philip ; Köck, Thomas LU and Mulder, Hindrik LU
(2011)
In Biochemical Journal
435.
p.277-284
- Abstract
- Insulin secretion from pancreatic beta-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 beta-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... (More)
- Insulin secretion from pancreatic beta-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 beta-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 beta-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-1 alpha (hypoxia-inducible factor 1 alpha). The relevance of a similar perturbation for human T2D was suggested by increased expression of HIF-1 alpha target genes in islets from T2D patients. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1925543
- author
- Spégel, Peter
LU
; Malmgren, Siri
LU
; Sharoyko, Vladimir
LU
; Newsholme, Philip
; Köck, Thomas
LU
and Mulder, Hindrik
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- hypoxia-inducible factor (HIF), mitochondria, pancreatic islet, insulin, Type 2 diabetes (T2D)
- in
- Biochemical Journal
- volume
- 435
- pages
- 277 - 284
- publisher
- Portland Press
- external identifiers
-
- wos:000289182100026
- scopus:79952821873
- pmid:21208194
- ISSN
- 0264-6021
- DOI
- 10.1042/BJ20100655
- language
- English
- LU publication?
- yes
- id
- 7a0aacd3-8fe3-4a79-ae21-da21d061ec24 (old id 1925543)
- date added to LUP
- 2016-04-01 15:01:02
- date last changed
- 2022-04-22 06:20:26
@article{7a0aacd3-8fe3-4a79-ae21-da21d061ec24,
abstract = {{Insulin secretion from pancreatic beta-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 beta-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 beta-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-1 alpha (hypoxia-inducible factor 1 alpha). The relevance of a similar perturbation for human T2D was suggested by increased expression of HIF-1 alpha target genes in islets from T2D patients.}},
author = {{Spégel, Peter and Malmgren, Siri and Sharoyko, Vladimir and Newsholme, Philip and Köck, Thomas and Mulder, Hindrik}},
issn = {{0264-6021}},
keywords = {{hypoxia-inducible factor (HIF); mitochondria; pancreatic islet; insulin; Type 2 diabetes (T2D)}},
language = {{eng}},
pages = {{277--284}},
publisher = {{Portland Press}},
series = {{Biochemical Journal}},
title = {{Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal beta-cell lines}},
url = {{https://lup.lub.lu.se/search/files/4301084/1951937.pdf}},
doi = {{10.1042/BJ20100655}},
volume = {{435}},
year = {{2011}},
}