Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes.

Molecular Endocrinology
Beatrice T YangCharlotte Ling

Abstract

Mutations in pancreatic duodenal homeobox 1 (PDX-1) can cause a monogenic form of diabetes (maturity onset diabetes of the young 4) in humans, and silencing Pdx-1 in pancreatic β-cells of mice causes diabetes. However, it is not established whether epigenetic alterations of PDX-1 influence type 2 diabetes (T2D) in humans. Here we analyzed mRNA expression and DNA methylation of PDX-1 in human pancreatic islets from 55 nondiabetic donors and nine patients with T2D. We further studied epigenetic regulation of PDX-1 in clonal β-cells. PDX-1 expression was decreased in pancreatic islets from patients with T2D compared with nondiabetic donors (P = 0.0002) and correlated positively with insulin expression (rho = 0.59, P = 0.000001) and glucose-stimulated insulin secretion (rho = 0.41, P = 0.005) in the human islets. Ten CpG sites in the distal PDX-1 promoter and enhancer regions exhibited significantly increased DNA methylation in islets from patients with T2D compared with nondiabetic donors. DNA methylation of PDX-1 correlated negatively with its gene expression in the human islets (rho = -0.64, P = 0.0000029). Moreover, methylation of the human PDX-1 promoter and enhancer regions suppressed reporter gene expression in clonal β-cell...Continue Reading

References

Nov 5, 1997·Nature Genetics·D A StoffersJ F Habener
Apr 20, 2001·The Journal of Biological Chemistry·H WangC B Wollheim
Jan 10, 2002·The Journal of Biological Chemistry·Marcela BrissovaAlvin C Powers
Feb 9, 2002·European Journal of Endocrinology·Hongxiang Hui, Riccardo Perfetti
Dec 12, 2002·Diabetes·Danielle MelloulErol Cerasi
Dec 28, 2002·Diabetes·Alexandra E ButlerPeter C Butler
May 10, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marta L HribalGiorgio Sesti
Nov 9, 2004·Current Opinion in Genetics & Development·Suyinn Chong, Emma Whitelaw
May 18, 2005·Biochemical and Biophysical Research Communications·Hirofumi NoguchiSusan Bonner-Weir
Jun 4, 2005·Science·Matthew D AnwayMichael K Skinner
Oct 30, 2007·Epigenetics : Official Journal of the DNA Methylation Society·Maja Klug, Michael Rehli
Nov 13, 2007·Diabetologia·G ParnaudP A Halban
Sep 24, 2008·The Journal of Experimental Medicine·Assam El-OstaMichael Brownlee
Dec 8, 2009·Science·Anders H RosengrenErik Renström
Feb 2, 2010·Nature Genetics·Kyle J GaultonJorge Ferrer
Feb 26, 2010·Genome Research·Reena BhandareKlaus H Kaestner
Sep 9, 2010·Genesis : the Journal of Genetics and Development·Junghun SongQingchun Tong
Mar 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ionel SandoviciSusan E Ozanne
Apr 19, 2011·Developmental Cell·Sangeeta DhawanAnil Bhushan
Jun 18, 2011·Nature Reviews. Genetics·Étienne DanchinSimon Blanchet

❮ Previous
Next ❯

Citations

Aug 3, 2013·Current Diabetes Reports·Cecile Haumaitre
Jul 31, 2013·PloS One·Eliete Dalla Corte FrantzCarlos Alberto Mandarim-de-Lacerda
Jun 3, 2014·Current Environmental Health Reports·Guoying WangXiaobin Wang
Dec 24, 2013·Diabetologia·Nuria C Bramswig, Klaus H Kaestner
Sep 24, 2014·Trends in Endocrinology and Metabolism : TEM·Dario F De Jesus, Rohit N Kulkarni
Feb 1, 2014·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Y SakarM Covasa
Mar 7, 2013·Cellular and Molecular Life Sciences : CMLS·Ionel SandoviciMiguel Constância
Oct 24, 2014·Biology·Vichithra R B LiyanageJames R Davie
May 30, 2015·Diabetes·Joanne C McNelisJerrold M Olefsky
Oct 9, 2015·Molecular Nutrition & Food Research·Celina Carvalho BorgesMarcia Barbosa Aguila
Nov 5, 2013·Critical Reviews in Oncology/hematology·Heidrun KarlicMichael Pfeilstöcker
Sep 10, 2013·Seminars in Nephrology·Marpadga A ReddyRama Natarajan
Dec 25, 2015·Drug Discovery Today·Andrix O ArguellesMahua Choudhury
Mar 31, 2015·Cell·Oliver J Rando, Rebecca A Simmons
Dec 24, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Evans Quilichini, Cécile Haumaitre
Nov 29, 2013·Mass Spectrometry Reviews·Ed Dudley, Liz Bond
Dec 3, 2014·Nutrition·Francielle Graus-NunesVanessa Souza-Mello
Sep 16, 2015·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Tasnim Dayeh, Charlotte Ling
Apr 7, 2015·Acta Diabetologica·Gregory Alexander RacitiFrancesco Béguinot
Aug 25, 2015·Frontiers in Genetics·Divya Sri Priyanka TallapragadaGiriraj R Chandak
Dec 30, 2014·Molecular Aspects of Medicine·Emilyn U AlejandroErnesto Bernal-Mizrachi
Sep 18, 2012·Molecular Aspects of Medicine·Kyle J Hewitt, Jonathan A Garlick
May 2, 2014·Annals of Medicine·Vanessa Derenji Ferreira de MelloMatti Uusitupa
Nov 15, 2014·Cell Biochemistry and Biophysics·Chiranjib ChakrabortyGovindasamy Agoramoorthy
Dec 12, 2013·Molecular Metabolism·Robert Wolfgang SchwenkAnnette Schürmann
Apr 2, 2015·Clinical Epigenetics·Gidon ToperoffAsaf Hellman
Jan 30, 2015·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·D Scott KehlerTodd A Duhamel

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Biomarkers for Type 2 Diabetes

Biomarkers can help understand chronic diseases and assist in risk prediction for prevention and early detection of diseases. Here is the latest research on biomarkers in type 2 diabetes, a disease in which the body is unable to produce or properly use insulin.