Exocytosis of insulin promotes insulin gene transcription via the insulin receptor/PI-3 kinase/p70 s6 kinase and CaM kinase pathways

Ingo B. Leibiger, Barbara Leibiger, Tilo Moede, Per Olof Berggren

Research output: Contribution to journalArticle

238 Scopus citations

Abstract

The control of glucose homeostasis by insulin requires, in addition to the glucose-induced insulin release, a highly dynamic control of insulin biosynthesis. Although elevated glucose concentrations have been shown to trigger insulin biosynthesis at the levels of transcription and translation, the molecular mechanisms underlying the immediate transcriptional control are poorly understood. By investigating signal transduction pathways involved in the "glucose-dependent" transcriptional control, thereby analyzing endogenous (prepro)insulin mRNA levels and monitoring on-line insulin promoter-driven GFP expression, we provide, for the first time, evidence that physiologically stimulated insulin secretion from the pancreatic β cell promotes insulin biosynthesis by enhancing insulin gene transcription in an autocrine manner. We show that secreted insulin acts via β-cell insulin receptors and up-regulates insulin gene transcription by signaling through the IRS-2/PI-3 kinase/p70 s6k and CaM kinase pathways.

Original languageEnglish (US)
Pages (from-to)933-938
Number of pages6
JournalMolecular Cell
Volume1
Issue number6
DOIs
StatePublished - May 1998

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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