Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic β cells

Barbara Leibiger, Ingo B. Leibiger, Tilo Moede, Sabine Kemper, Rohit N. Kulkarni, C. Ronald Kahn, Lina Moitoso De Vargas, Per Olof Berggren

Research output: Contribution to journalArticle

205 Scopus citations

Abstract

Insulin signaling is mediated by a complex network of diverging and converging pathways, with alternative proteins and isoforms at almost every step in the process. We show here that insulin activates the transcription of its own gene and that of the β cell glucokinase gene (βGK) by different mechanisms. Whereas insulin gene transcription is promoted by signaling through insulin receptor A type (Ex11-), PI3K class Ia, and p70s6k, insulin stimulates the βGK gene by signaling via insulin receptor B type (Ex11+), PI3K class II-like activity, and PKB (c-Akt). Our data provide evidence for selectivity in insulin action via the two isoforms of the insulin receptor, the molecular basis being preferential signaling through different PI3K and protein kinases.

Original languageEnglish (US)
Pages (from-to)559-570
Number of pages12
JournalMolecular Cell
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Leibiger, B., Leibiger, I. B., Moede, T., Kemper, S., Kulkarni, R. N., Kahn, C. R., De Vargas, L. M., & Berggren, P. O. (2001). Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic β cells. Molecular Cell, 7(3), 559-570. https://doi.org/10.1016/S1097-2765(01)00203-9