RGD Reference Report - Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. - Rat Genome Database

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

Authors: Ling, C  Del Guerra, S  Lupi, R  Ronn, T  Granhall, C  Luthman, H  Masiello, P  Marchetti, P  Groop, L  Del Prato, S 
Citation: Ling C, etal., Diabetologia. 2008 Apr;51(4):615-22. Epub 2008 Feb 13.
RGD ID: 2311391
Pubmed: PMID:18270681   (View Abstract at PubMed)
PMCID: PMC2270364   (View Article at PubMed Central)
DOI: DOI:10.1007/s00125-007-0916-5   (Journal Full-text)

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




  
Object Symbol
Species
Term
Qualifier
Evidence
With
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Source
Original Reference(s)
PPARGC1AHumanExperimental Diabetes Mellitus  ISORGD:620925mRNA:decreased expression:pancreatic isletRGD 
Ppargc1aRatExperimental Diabetes Mellitus  IEP mRNA:decreased expression:pancreatic isletRGD 
Ppargc1aMouseExperimental Diabetes Mellitus  ISORGD:620925mRNA:decreased expression:pancreatic isletRGD 
PPARGC1AHumantype 2 diabetes mellitus  IAGP DNA:polymorphism:exon:p.G482S (human)RGD 
Ppargc1aRattype 2 diabetes mellitus  ISORGD:1342674DNA:polymorphism:exon:p.G482S (human)RGD 
Ppargc1aMousetype 2 diabetes mellitus  ISORGD:1342674DNA:polymorphism:exon:p.G482S (human)RGD 


Genes (Rattus norvegicus)
Ppargc1a  (PPARG coactivator 1 alpha)

Genes (Mus musculus)
Ppargc1a  (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha)

Genes (Homo sapiens)
PPARGC1A  (PPARG coactivator 1 alpha)