Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07070-z |
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| author | Ligia Akemi Kiyuna Kishore Alagere Krishnamurthy Esther B. Homan Miriam Langelaar-Makkinje Albert Gerding Trijnie Bos Dorenda Oosterhuis Ruben J. Overduin Andrea B. Schreuder Vincent E. de Meijer Peter Olinga Terry G. J. Derks Karen van Eunen Barbara M. Bakker Maaike H. Oosterveer |
| author_facet | Ligia Akemi Kiyuna Kishore Alagere Krishnamurthy Esther B. Homan Miriam Langelaar-Makkinje Albert Gerding Trijnie Bos Dorenda Oosterhuis Ruben J. Overduin Andrea B. Schreuder Vincent E. de Meijer Peter Olinga Terry G. J. Derks Karen van Eunen Barbara M. Bakker Maaike H. Oosterveer |
| author_sort | Ligia Akemi Kiyuna |
| collection | DOAJ |
| description | Abstract 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 13C 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. |
| format | Article |
| id | doaj-art-80c7e8fec88b4b8f9ec36708526d3646 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-80c7e8fec88b4b8f9ec36708526d36462024-11-10T12:39:08ZengNature PortfolioCommunications Biology2399-36422024-11-017111310.1038/s42003-024-07070-zPrecision-cut liver slices as an ex vivo model to assess impaired hepatic glucose productionLigia Akemi Kiyuna0Kishore Alagere Krishnamurthy1Esther B. Homan2Miriam Langelaar-Makkinje3Albert Gerding4Trijnie Bos5Dorenda Oosterhuis6Ruben J. Overduin7Andrea B. Schreuder8Vincent E. de Meijer9Peter Olinga10Terry G. J. Derks11Karen van Eunen12Barbara M. Bakker13Maaike H. Oosterveer14Department of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Laboratory Medicine, University of Groningen, University Medical Center GroningenDepartment of Pharmaceutical Technology and Biopharmacy, University of GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenSection of HPB Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center GroningenDepartment of Pharmaceutical Technology and Biopharmacy, University of GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenDepartment of Pediatrics, University of Groningen, University Medical Center GroningenAbstract 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 13C 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.https://doi.org/10.1038/s42003-024-07070-z |
| spellingShingle | Ligia Akemi Kiyuna Kishore Alagere Krishnamurthy Esther B. Homan Miriam Langelaar-Makkinje Albert Gerding Trijnie Bos Dorenda Oosterhuis Ruben J. Overduin Andrea B. Schreuder Vincent E. de Meijer Peter Olinga Terry G. J. Derks Karen van Eunen Barbara M. Bakker Maaike H. Oosterveer Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production Communications Biology |
| title | Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production |
| title_full | Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production |
| title_fullStr | Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production |
| title_full_unstemmed | Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production |
| title_short | Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production |
| title_sort | precision cut liver slices as an ex vivo model to assess impaired hepatic glucose production |
| url | https://doi.org/10.1038/s42003-024-07070-z |
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