Short-term regulation of insulin gene transcription by glucose

Barbara Leibiger, Tilo Moede, Thomas Schwarz, Graham R. Brown, Martin Köhler, Ingo B. Leibiger, Per Olof Berggren

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)9307-9312
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number16
DOIs
StatePublished - Aug 4 1998

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    Leibiger, B., Moede, T., Schwarz, T., Brown, G. R., Köhler, M., Leibiger, I. B., & Berggren, P. O. (1998). Short-term regulation of insulin gene transcription by glucose. Proceedings of the National Academy of Sciences of the United States of America, 95(16), 9307-9312. https://doi.org/10.1073/pnas.95.16.9307