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Unique and Shared Metabolic Regulation in Clonal β-cells and Primary Islets Derived from Rat Revealed by Metabolomics Analysis.

Spégel, Peter LU ; Andersson, Lotta LU ; Storm, Petter LU ; Sharoyko, Vladimir LU ; Göhring, Isabel LU ; Rosengren, Anders LU and Mulder, Hindrik LU (2015) In Endocrinology 156(6). p.1995-2005
Abstract
As models for β-cell metabolism, rat islets are, to some extent, a, heterogeneous cell-population stressed by the islet isolation procedure, while rat-derived clonal β-cells exhibit a tumor-like phenotype. To describe to what extent either of these models reflect normal cellular metabolism, we compared metabolite profiles and gene expression in rat islets and the INS-1 832/13 line, a widely used clonal β-cell model. We found that insulin secretion and metabolic regulation provoked by glucose were qualitatively similar in these β-cell models. However, rat islets exhibited a more pronounced glucose-provoked increase of glutamate, glycerol-3-phosphate, succinate and lactate levels while INS-1 832/13 cells showed a higher glucose-elicited... (More)
As models for β-cell metabolism, rat islets are, to some extent, a, heterogeneous cell-population stressed by the islet isolation procedure, while rat-derived clonal β-cells exhibit a tumor-like phenotype. To describe to what extent either of these models reflect normal cellular metabolism, we compared metabolite profiles and gene expression in rat islets and the INS-1 832/13 line, a widely used clonal β-cell model. We found that insulin secretion and metabolic regulation provoked by glucose were qualitatively similar in these β-cell models. However, rat islets exhibited a more pronounced glucose-provoked increase of glutamate, glycerol-3-phosphate, succinate and lactate levels while INS-1 832/13 cells showed a higher glucose-elicited increase in glucose-6-phosphate, alanine, isocitrate, and α-ketoglutarate levels. Glucose induced a decrease in levels of γ-aminobutyrate (GABA) and aspartate in rat islets and INS-1 832/13 cells, respectively. Genes with cellular functions related to proliferation and the cell cycle were more highly expressed in the INS-1 832/13 cells. Most metabolic pathways that were differentially expressed included GABA metabolism, in line with altered glucose responsiveness of GABA. Also, lactate dehydrogenase A, which is normally expressed at low levels in mature β-cells, was more abundant in rat islets than in INS-1 832/13 cells, confirming the finding of elevated glucose-provoked lactate production in the rat islets. Overall, our results suggest that metabolism in rat islets and INS-1 832/13 cells is qualitatively similar, albeit with quantitative differences. Differences may be accounted for by cellular heterogeneity of islets and proliferation of the INS-1 832/13 cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrinology
volume
156
issue
6
pages
1995 - 2005
publisher
Endocrine Society
external identifiers
  • pmid:25774549
  • wos:000358435400010
  • scopus:84930447586
ISSN
0013-7227
DOI
10.1210/en.2014-1391
language
English
LU publication?
yes
id
4c9b4051-d5a4-430e-9fce-a26f9172a075 (old id 5258564)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25774549?dopt=Abstract
date added to LUP
2015-04-03 20:14:40
date last changed
2017-01-01 03:47:55
@article{4c9b4051-d5a4-430e-9fce-a26f9172a075,
  abstract     = {As models for β-cell metabolism, rat islets are, to some extent, a, heterogeneous cell-population stressed by the islet isolation procedure, while rat-derived clonal β-cells exhibit a tumor-like phenotype. To describe to what extent either of these models reflect normal cellular metabolism, we compared metabolite profiles and gene expression in rat islets and the INS-1 832/13 line, a widely used clonal β-cell model. We found that insulin secretion and metabolic regulation provoked by glucose were qualitatively similar in these β-cell models. However, rat islets exhibited a more pronounced glucose-provoked increase of glutamate, glycerol-3-phosphate, succinate and lactate levels while INS-1 832/13 cells showed a higher glucose-elicited increase in glucose-6-phosphate, alanine, isocitrate, and α-ketoglutarate levels. Glucose induced a decrease in levels of γ-aminobutyrate (GABA) and aspartate in rat islets and INS-1 832/13 cells, respectively. Genes with cellular functions related to proliferation and the cell cycle were more highly expressed in the INS-1 832/13 cells. Most metabolic pathways that were differentially expressed included GABA metabolism, in line with altered glucose responsiveness of GABA. Also, lactate dehydrogenase A, which is normally expressed at low levels in mature β-cells, was more abundant in rat islets than in INS-1 832/13 cells, confirming the finding of elevated glucose-provoked lactate production in the rat islets. Overall, our results suggest that metabolism in rat islets and INS-1 832/13 cells is qualitatively similar, albeit with quantitative differences. Differences may be accounted for by cellular heterogeneity of islets and proliferation of the INS-1 832/13 cells.},
  author       = {Spégel, Peter and Andersson, Lotta and Storm, Petter and Sharoyko, Vladimir and Göhring, Isabel and Rosengren, Anders and Mulder, Hindrik},
  issn         = {0013-7227},
  language     = {eng},
  number       = {6},
  pages        = {1995--2005},
  publisher    = {Endocrine Society},
  series       = {Endocrinology},
  title        = {Unique and Shared Metabolic Regulation in Clonal β-cells and Primary Islets Derived from Rat Revealed by Metabolomics Analysis.},
  url          = {http://dx.doi.org/10.1210/en.2014-1391},
  volume       = {156},
  year         = {2015},
}