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Transcriptional networks controlling pancreatic development and beta cell function

Journal

DIABETOLOGIA
Volume 47, Issue 4, Pages 597-613

Publisher

SPRINGER
DOI: 10.1007/s00125-004-1368-9

Keywords

chromatin immunoprecipitation; gene networks; Haplo-insufficiency; Hnf1 alpha; Hnf beta; Hnf4 alpha; islets of Langerhans; MODY1; MODY3; Ngn3; Nkx2.2; Pdx1; Stem cells; Type 1 diabetes mellitus; Type 2 diabetes mellitus

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Transcription factors provide the genetic instructions that drive pancreatic development and enable mature beta cells to function properly. To understand fully how this is accomplished, it is necessary to unravel the regulatory networks formed by transcription factors acting on their genomic targets. This article discusses recent advances in our understanding of how transcriptional networks control early pancreas organogenesis, embryonic endocrine cell formation and the differentiated function of adult beta cells. We discuss how mutations in several transcription factor genes involved in such networks cause Maturity onset diabetes of the young (MODY). Finally, we propose that pancreatic gene programs might be manipulated to generate beta cells or to enhance the function of existing beta cells, thereby providing a possible treatment of different forms of diabetes.

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