Unique and Shared Metabolic Regulation in Clonal β-Cells and Primary Islets Derived From Rat Revealed by Metabolomics Analysis

Endocrinology
Peter SpégelHindrik Mulder

Abstract

As models for β-cell metabolism, rat islets are, to some extent, a, heterogeneous cell population stressed by the islet isolation procedure, whereas 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, whereas 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 dehyd...Continue Reading

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Citations

Jun 28, 2015·Archives of Biochemistry and Biophysics·Jessica R GoodingChristopher B Newgard
Dec 13, 2016·FEBS Letters·Lotta E AnderssonPeter Spégel
Feb 13, 2018·The Journal of Endocrinology·Malin FexHindrik Mulder
Sep 2, 2016·Physiological Reviews·David G Nicholls
Jul 22, 2019·Journal of Molecular Biology·Peter Spégel, Hindrik Mulder
Feb 27, 2021·Cellular and Molecular Bioengineering·Ryland D MortlockStacey D Finley

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