Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production.

Autor: Kiyuna LA; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Krishnamurthy KA; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Homan EB; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Langelaar-Makkinje M; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Gerding A; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Bos T; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Oosterhuis D; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands., Overduin RJ; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Schreuder AB; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., de Meijer VE; Section of HPB Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Olinga P; Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands., Derks TGJ; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van Eunen K; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Bakker BM; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. b.m.bakker01@umcg.nl., Oosterveer MH; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. moosterveer@hotmail.com.; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. moosterveer@hotmail.com.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Nov 09; Vol. 7 (1), pp. 1479. Date of Electronic Publication: 2024 Nov 09.
DOI: 10.1038/s42003-024-07070-z
Abstrakt: Fasting hypoglycemia is a severe and incompletely understood symptom of various inborn errors of metabolism (IEM). Precision-cut liver slices (PCLS) represent a promising model for studying glucose production ex vivo. This study quantified the net glucose production of human and murine PCLS in the presence of different gluconeogenic precursors. Dihydroxyacetone-supplemented slices from the fed mice yielded the highest rate, further stimulated by forskolin and dibutyryl-cAMP. Moreover, using 13 C isotope tracing, we assessed the contribution of glycogenolysis and gluconeogenesis to net glucose production over time. Pharmacological inhibition of the glucose 6-phosphate transporter SLC37A4 markedly reduced net glucose production and increased lactate secretion and glycogen storage, while glucose production was completely abolished in PCLS from glycogen storage disease type Ia and Ib patients. In conclusion, this study identifies PCLS as an effective ex vivo model to study hepatic glucose production and opens opportunities for its future application in IEM research and beyond.
(© 2024. The Author(s).)
Databáze: MEDLINE
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