Integrative mitogenic role of protein kinase B/Akt in beta-cells

Ann N Y Acad Sci. 2000;921:242-50. doi: 10.1111/j.1749-6632.2000.tb06972.x.

Abstract

Protein kinase B/Akt (PKB/Akt) is activated by phosphatidylinositol 3-kinase (PI 3-K) and is a central mediator of cellular proliferation and protection against apoptosis. Insulin, insulin-like growth factor (IGF-1), and glucagon-like peptide-1 (GLP-1) act as glucose-dependent growth factors for pancreatic beta-cells. We assessed signaling pathways and stimulation patterns of PKB/Akt activation by these ligands in the beta-cell line INS-1. Insulin, IGF-1, and GLP-1 induced distinctive time dependent, dose dependent, and glucose dependent phosphorylation of PKB/Akt. Insulin and IGF-1 stimulated PI 3-K activity was mainly associated with insulin receptor substrate (IRS) isoforms IRS-1 and IRS-2 and less so with the IRS-isoform Grb-2 associated binder-1 (Gab-1). In contrast, GLP-1 induced PI 3-K activity mainly in Gab-1 and also in IRS-2 immunoprecipitates, although in an attenuated kinetic. Thus, activation pathways of PKB/Akt by insulin, IGF-1, and GLP-1 converge at the level of IRS-isoforms and PI 3-K inducing differential activation of PKB/Akt. These data indicate an essential role of PKB/Akt in regulation of beta-cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Line
  • Enzyme Activation / drug effects
  • Glucagon / pharmacology
  • Glucagon-Like Peptide 1
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / pharmacology
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mitogens / metabolism*
  • Peptide Fragments / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Precursors / pharmacology
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Signal Transduction

Substances

  • Insulin
  • Mitogens
  • Peptide Fragments
  • Protein Precursors
  • Proto-Oncogene Proteins
  • Insulin-Like Growth Factor I
  • Glucagon-Like Peptide 1
  • Glucagon
  • Phosphatidylinositol 3-Kinases
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt