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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5258564
- author
- Spégel, Peter
LU
; Andersson, Lotta
LU
; Storm, Petter
LU
; Sharoyko, Vladimir
LU
; Göhring, Isabel
LU
; Rosengren, Anders
LU
and Mulder, Hindrik
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Endocrinology
- volume
- 156
- issue
- 6
- pages
- 1995 - 2005
- publisher
- Oxford University Press
- external identifiers
-
- pmid:25774549
- wos:000358435400010
- scopus:84930447586
- pmid:25774549
- 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
- 2016-04-01 10:40:13
- date last changed
- 2024-02-05 10:39:23
@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 = {{Oxford University Press}},
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}},
doi = {{10.1210/en.2014-1391}},
volume = {{156}},
year = {{2015}},
}