The Insulin Gene Contains Multiple Transcriptional Elements That Respond to Glucose

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1994 Jun 1

PMID 8196645

Citations 37

Authors

M S German

J Wang

Affiliations

Soon will be listed here.

Abstract

The beta cells in the pancreatic islets of Langerhans increase insulin gene transcription in response to increased glucose concentration. We have mapped sequences within the rat insulin I gene 5'-flanking DNA (rInsI promoter) that direct this transcriptional response to glucose. When linked to chloramphenicol acetyltransferase and expressed in cultured beta cells, no single mutation of the rInsI promoter removes its ability to respond to glucose, although several mutations cause marked reductions in basal chloramphenicol acetyltransferase expression. A 50-bp sequence isolated from the rInsI promoter, the Far-FLAT minienhancer, can confer glucose responsiveness to nonresponsive promoters. Fine mapping of this minienhancer further localizes a glucose response to the sequence GGCCATCTGGCC, or the Far element. Nuclear extracts from islets grown in various glucose concentrations demonstrate a glucose-stimulated increase in a protein complex that binds the Far element and contains the transcription factors Pan-1 and Pan-2. Overexpression of intact or partially deleted Pan-1 ablates the Far-directed transcriptional response to glucose. We conclude that the full glucose response of the insulin promoter involves the interaction of multiple sequence elements. Part of this response, however, results from activation of a complex binding at the Far element.

Citing Articles

Glucose Controls the Expression of Polypyrimidine Tract-Binding Protein 1 via the Insulin Receptor Signaling Pathway in Pancreatic β Cells.

Jeong D, Heo S, Han J, Lee E, Kulkarni R, Kim W Mol Cells. 2018; 41(10):909-916.

PMID: 30165730 PMC: 6199568. DOI: 10.14348/molcells.2018.0147.

Glucose regulates MafA transcription factor abundance and insulin gene expression by inhibiting AMP-activated protein kinase in pancreatic β-cells.

Iwaoka R, Kataoka K J Biol Chem. 2018; 293(10):3524-3534.

PMID: 29348175 PMC: 5846144. DOI: 10.1074/jbc.M117.817932.

Role of pancreatic transcription factors in maintenance of mature β-cell function.

Kaneto H, Matsuoka T Int J Mol Sci. 2015; 16(3):6281-97.

PMID: 25794287 PMC: 4394532. DOI: 10.3390/ijms16036281.

Cooperation between HMGA1, PDX-1, and MafA is Essential for Glucose-Induced Insulin Transcription in Pancreatic Beta Cells.

Arcidiacono B, Iiritano S, Chiefari E, Brunetti F, Gu G, Foti D Front Endocrinol (Lausanne). 2015; 5:237.

PMID: 25628604 PMC: 4292585. DOI: 10.3389/fendo.2014.00237.

Thermodynamic and structural determinants of differential Pdx1 binding to elements from the insulin and IAPP promoters.

Bastidas M, Showalter S J Mol Biol. 2013; 425(18):3360-77.

PMID: 23796517 PMC: 3800017. DOI: 10.1016/j.jmb.2013.06.011.

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