title: Unique and Shared Metabolic Regulation in Clonal β-Cells and Primary Islets Derived From Rat Revealed by Metabolomics Analysis.
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 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.
authors.affiliation: Unit of Molecular Metabolism (P.S., L.E.A., V.S., I.G., H.M.), Lund University Diabetes Centre, Clinical Research Center, Skåne University Hospital, and Lund University Diabetes Centre (P.S., A.H.R.), Clinical Research Center, Skåne University Hospital, 205 02 Malmö, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Spégel
authors.forename: Lotta E
authors.initials: LE
authors.lastname: Andersson
authors.forename: Petter
authors.initials: P
authors.lastname: Storm
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sharoyko
authors.forename: Isabel
authors.initials: I
authors.lastname: Göhring
authors.forename: Anders H
authors.initials: AH
authors.lastname: Rosengren
authors.forename: Hindrik
authors.initials: H
authors.lastname: Mulder
mesh_terms: D000818:Animals; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D005947:Glucose