Short-term regulation of insulin gene transcription

2002 ◽  
Vol 30 (2) ◽  
pp. 312-317 ◽  
Author(s):  
B. Leibiger ◽  
T. Moede ◽  
S. Uhles ◽  
P.-O. Berggren ◽  
I. B. Leibiger
Keyword(s):  
Insulin Secretion ◽  
Gene Transcription ◽  
Insulin Gene ◽  
Current View ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Short Term ◽  
Major Nutrient ◽  
Glucose Metabolites ◽  
Insulin Gene Transcription

Short-term regulation of insulin gene transcription is still a matter of debate. However, an increasing body of evidence shows that insulin gene transcription is affected by signals, such as incretins, glucose metabolites, intracellular Ca2+, and by insulin secreted from pancreatic β-cells, all supporting the concept of an immediate response resulting in insulin gene transcription following food-uptake. The present review aims to summarize the current view on the mechanisms underlying the up-regulation of insulin gene transcription in response to glucose, the major nutrient factor in insulin secretion and biosynthesis.

scholarly journals Regulation of Insulin Gene Transcription by ERK1 and ERK2 in Pancreatic β Cells

2003 ◽  
Vol 278 (35) ◽  
pp. 32969-32977 ◽  
Author(s):  
Shih Khoo ◽  
Steven C. Griffen ◽  
Ying Xia ◽  
Richard J. Baer ◽  
Michael S. German ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Insulin Gene ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Insulin Gene Transcription

scholarly journals Covalent Histone Modifications Underlie the Developmental Regulation of Insulin Gene Transcription in Pancreatic β Cells

2003 ◽  
Vol 278 (26) ◽  
pp. 23617-23623 ◽  
Author(s):  
Swarup K. Chakrabarti ◽  
Joshua Francis ◽  
Suzanne M. Ziesmann ◽  
James C. Garmey ◽  
Raghavendra G. Mirmira
Keyword(s):  
Gene Transcription ◽  
Histone Modifications ◽  
Developmental Regulation ◽  
Insulin Gene ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Covalent Histone Modifications ◽  
Insulin Gene Transcription

Nitric oxide stimulates insulin gene transcription in pancreatic β-cells

2007 ◽  
Vol 353 (4) ◽  
pp. 1011-1016 ◽  
Author(s):  
S.C. Campbell ◽  
H. Richardson ◽  
W.F. Ferris ◽  
C.S. Butler ◽  
W.M. Macfarlane
Keyword(s):  
Nitric Oxide ◽  
Gene Transcription ◽  
Insulin Gene ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Insulin Gene Transcription

scholarly journals Short-term regulation of insulin gene transcription by glucose

1998 ◽  
Vol 95 (16) ◽  
pp. 9307-9312 ◽  
Author(s):  
Barbara Leibiger ◽  
Tilo Moede ◽  
Thomas Schwarz ◽  
Graham R. Brown ◽  
Martin Köhler ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Transcriptional Control ◽  
Insulin Gene ◽  
Insulin Biosynthesis ◽  
Short Term ◽  
Glucose Stimulation ◽  
Insulin Producing Cells ◽  
Elevated Glucose ◽  
Insulinoma Cells ◽  
Insulin Gene Transcription

Whereas short-term regulation of insulin biosynthesis at the level of translation is well accepted, glucose-dependent transcriptional control is still believed to be a long-term effect occurring after more than 2 hr of glucose stimulation. Because pancreatic β cells are exposed to elevated glucose levels for minutes rather than hours after food uptake, we hypothesized the existence of a short-term transcriptional control. By studying the dynamics of newly synthesized (prepro)insulin RNA and by employing on-line monitoring of gene expression in single, insulin-producing cells, we were able to provide convincing evidence that insulin gene transcription indeed is affected by glucose within minutes. Exposure of insulinoma cells and isolated pancreatic islets to elevated glucose for only 15 min resulted in a 2- to 5-fold elevation in (prepro)insulin mRNA levels within 60–90 min. Similarly, insulin promoter-driven green fluorescent protein expression in single insulin-producing cells was significantly enhanced after transient glucose stimulation. Thus, short-term signaling, such as that involved in insulin secretion, also may regulate insulin gene transcription.

scholarly journals Insulin Gene Transcription Is Mediated by Interactions between the p300 Coactivator and PDX-1, BETA2, and E47

2002 ◽  
Vol 22 (2) ◽  
pp. 412-420 ◽  
Author(s):  
Yi Qiu ◽  
Min Guo ◽  
Suming Huang ◽  
Roland Stein
Keyword(s):  
Dna Binding ◽  
Rna Polymerase Ii ◽  
Gene Transcription ◽  
Present Report ◽  
Amino Acid Sequences ◽  
Insulin Gene ◽  
Homeodomain Protein ◽  
Β Cells ◽  
Β Cell ◽  
Insulin Gene Transcription

ABSTRACT Pancreatic β-cell-type-specific expression of the insulin gene requires both ubiquitous and cell-enriched activators, which are organized within the enhancer region into a network of protein-protein and protein-DNA interactions to promote transcriptional synergy. Protein-protein-mediated communication between DNA-bound activators and the RNA polymerase II transcriptional machinery is inhibited by the adenovirus E1A protein as a result of E1A’s binding to the p300 coactivator. E1A disrupts signaling between the non-DNA-binding p300 protein and the basic helix-loop-helix DNA-binding factors of insulin’s E-element activator (i.e., the islet-enriched BETA2 and generally distributed E47 proteins), as well as a distinct but unidentified enhancer factor. In the present report, we show that E1A binding to p300 prevents activation by insulin’s β-cell-enriched PDX-1 activator. p300 interacts directly with the N-terminal region of the PDX-1 homeodomain protein, which contains conserved amino acid sequences essential for activation. The unique combination of PDX-1, BETA2, E47, and p300 was shown to promote synergistic activation from a transfected insulin enhancer-driven reporter construct in non-β cells, a process inhibited by E1A. In addition, E1A inhibited the level of PDX-1 and BETA2 complex formation in β cells. These results indicate that E1A inhibits insulin gene transcription by preventing communication between the p300 coactivator and key DNA-bound activators, like PDX-1 and BETA2:E47.

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