Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion.

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Ling, CharlotteLund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Diabetes - epigenetik,Translational Muscle Research,Lund University Research Groups,Diabetes - Epigenetics (author)

Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion.

Article/chapterEnglish2008

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2008-02-13
Springer Science and Business Media LLC,2008

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LIBRIS-ID:oai:lup.lub.lu.se:06d93f63-4c04-4d5e-9777-bc69d1a56348
https://lup.lub.lu.se/record/1042001URI
https://doi.org/10.1007/s00125-007-0916-5DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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AIMS/HYPOTHESIS: Insulin secretion in pancreatic islets is dependent upon mitochondrial function and production of ATP. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator-1 alpha (protein PGC-1alpha; gene PPARGC1A) is a master regulator of mitochondrial genes and its expression is decreased and related to impaired oxidative phosphorylation in muscle from patients with type 2 diabetes. Whether it plays a similar role in human pancreatic islets is not known. We therefore investigated if PPARGC1A expression is altered in islets from patients with type 2 diabetes and whether this expression is influenced by genetic (PPARGC1A Gly482Ser polymorphism) and epigenetic (DNA methylation) factors. We also tested if experimental downregulation of PPARGC1A expression in human islets influenced insulin secretion. METHODS: The PPARGC1A Gly482Ser polymorphism was genotyped in human pancreatic islets from 48 non-diabetic and 12 type 2 diabetic multi-organ donors and related to PPARGC1A mRNA expression. DNA methylation of the PPARGC1A promoter was analysed in pancreatic islets from ten type 2 diabetic and nine control donors. Isolated human islets were transfected with PPARGC1A silencing RNA (siRNA). RESULTS: PPARGC1A mRNA expression was reduced by 90% (p < 0.005) and correlated with the reduction in insulin secretion in islets from patients with type 2 diabetes. After downregulation of PPARGC1A expression in human islets by siRNA, insulin secretion was reduced by 41% (p

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Del Guerra, S (author)
Lupi, R (author)
Rönn, TinaLund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Diabetes - epigenetik,Translational Muscle Research,Lund University Research Groups,Diabetes - Epigenetics(Swepub:lu)med-tar (author)
Granhall, CharlotteLund University,Lunds universitet,Genetik,Forskargrupper vid Lunds universitet,Genetics,Lund University Research Groups(Swepub:lu)endo-cgr (author)
Luthman, HolgerLund University,Lunds universitet,Genetik,Forskargrupper vid Lunds universitet,Genetics,Lund University Research Groups(Swepub:lu)endo-hlu (author)
Masiello, P (author)
Marchetti, P (author)
Groop, LeifLund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)endo-lgr (author)
Del Prato, S (author)
Translationell Muskel ForskningForskargrupper vid Lunds universitet (creator_code:org_t)

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In:Diabetologia: Springer Science and Business Media LLC51, s. 615-6221432-04280012-186X

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By the author/editor: Ling, Charlotte; Del Guerra, S; Lupi, R; Rönn, Tina; Granhall, Charlo ...; Luthman, Holger; show more...; Masiello, P; Marchetti, P; Groop, Leif; Del Prato, S; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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By the university: Lund University

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