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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005018naa a2200421 4500
001oai:lup.lub.lu.se:e3c30d9f-d6a9-4d36-9274-788b29e27447
003SwePub
008200116s2019 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/e3c30d9f-d6a9-4d36-9274-788b29e274472 URI
0247 a https://doi.org/10.2337/db18-09002 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Hall, Elinu Lund University,Lunds universitet,Skåne University Hospital4 aut0 (Swepub:lu)med-ehl
2451 0a Glucolipotoxicity alters insulin secretion via epigenetic changes in human islets
264 c 2019-08-16
264 1b American Diabetes Association,c 2019
520 a Type 2 diabetes (T2D) is characterized by insufficient insulin secretion and elevated glucose levels, often in combination with high levels of circulating fatty acids. Long-term exposure to high levels of glucose or fatty acids impair insulin secretion in pancreatic islets, which could partly be due to epigenetic alterations. We studied the effects of high concentrations of glucose and palmitate combined for 48 h (glucolipotoxicity) on the transcriptome, the epigenome, and cell function in human islets. Glucolipotoxicity impaired insulin secretion, increased apoptosis, and significantly (false discovery rate <5%) altered the expression of 1,855 genes, including 35 genes previously implicated in T2D by genomewide association studies (e.g., TCF7L2 and CDKN2B). Additionally, metabolic pathways were enriched for downregulated genes. Of the differentially expressed genes, 1,469 also exhibited altered DNA methylation (e.g., CDK1, FICD, TPX2, and TYMS). A luciferase assay showed that increased methylation of CDK1 directly reduces its transcription in pancreatic β-cells, supporting the idea that DNA methylation underlies altered expression after glucolipotoxicity. Follow-up experiments in clonal β-cells showed that knockdown of FICD and TPX2 alters insulin secretion. Together, our novel data demonstrate that glucolipotoxicity changes the epigenome in human islets, thereby altering gene expression and possibly exacerbating the secretory defect in T2D.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
7001 a Jönsson, Josefineu Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)jo7760jo
7001 a Ofori, Jones K.u Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)med-joi
7001 a Volkov, Petru Lund University,Lunds universitet,Skåne University Hospital4 aut0 (Swepub:lu)med-pvo
7001 a Perfilyev, Alexanderu Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)med-apy
7001 a Nitert, Marloes Dekkeru Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)medk-mad
7001 a Eliasson, Lenau Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)mphy-lel
7001 a Ling, Charlotteu Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)endo-cl0
7001 a Bacos, Karlu Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)medk-kb0
7102 a Lunds universitetb Skåne University Hospital4 org
7730 t Diabetesd : American Diabetes Associationg 68:10, s. 1965-1974q 68:10<1965-1974x 0012-1797x 1939-327X
8564 u http://dx.doi.org/10.2337/db18-0900y FULLTEXT
8564 u https://diabetes.diabetesjournals.org/content/diabetes/68/10/1965.full.pdf
8564 8u https://lup.lub.lu.se/record/e3c30d9f-d6a9-4d36-9274-788b29e27447
8564 8u https://doi.org/10.2337/db18-0900

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