Glucose regulation of insulin gene expression in pancreatic β-cells

Sreenath S. Andrali, Megan L. Smapley, Nathan L. Vanderford, Sabire Özcan

Research output: Contribution to journalReview articlepeer-review

161 Scopus citations

Abstract

Production and secretion of insulin from the β-cells of the pancreas is very crucial in maintaining normoglycaemia. This is achieved by tight regulation of insulin synthesis and exocytosis from the β-cells in response to changes in blood glucose levels. The synthesis of insulin is regt lated by blood glucose levels at the transcriptional and post-tianscriptional levels. Although many transcription factors have been implicated in the regulation of insulin gene transciiption, three β-cell-specific transcriptional regulators, Pdx-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation 1) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A), have been demonstrated to play a crucial role in glucose induction of insulin gene transcription and pancreatic β-cell function. These three transcription factors activate insulin gene expression in a co-ordinated and synergistic manner in response to increasing glucose levels. It has been shown that changes in glucose concentrations modulate the function of these β-cell transcription factors at multiple levels. These include changes in expression levels, subcellular localization, DNA-binding activity, transactivation capability and interaction with other proteins. Furthermore, all three transcription factors are able to induce insulin gene expression when expressed in non-β-cells, including liver and intestinal cells. The present review summarizes the recent findings on how glucose modulates the function of the β-cell transcription factors Pdx-1, NeuroD1 and MafA, and thereby tightly regulates insulin synthesis in accordance with blood glucose levels.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBiochemical Journal
Volume415
Issue number1
DOIs
StatePublished - Oct 1 2008

Keywords

  • Diabetes
  • Glucose
  • Insulin
  • NeuroD1 (neurogenic) differentiation 1)
  • Pancreatic and duodenal homeobox-1 (Pdx-1)
  • V-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MadfA)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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