Temporal coding of insulin action through multiplexing of the AKT pathway

Mol Cell. 2012 Jun 29;46(6):820-32. doi: 10.1016/j.molcel.2012.04.018. Epub 2012 May 24.


One of the unique characteristics of cellular signaling pathways is that a common signaling pathway can selectively regulate multiple cellular functions of a hormone; however, this selective downstream control through a common signaling pathway is poorly understood. Here we show that the insulin-dependent AKT pathway uses temporal patterns multiplexing for selective regulation of downstream molecules. Pulse and sustained insulin stimulations were simultaneously encoded into transient and sustained AKT phosphorylation, respectively. The downstream molecules, including ribosomal protein S6 kinase (S6K), glucose-6-phosphatase (G6Pase), and glycogen synthase kinase-3β (GSK3β) selectively decoded transient, sustained, and both transient and sustained AKT phosphorylation, respectively. Selective downstream decoding is mediated by the molecules' network structures and kinetics. Our results demonstrate that the AKT pathway can multiplex distinct patterns of blood insulin, such as pulse-like additional and sustained-like basal secretions, and the downstream molecules selectively decode secretion patterns of insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Glucose-6-Phosphatase / metabolism
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta
  • Insulin / metabolism*
  • Kinetics
  • Male
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction*


  • Insulin
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases
  • Glycogen Synthase Kinase 3
  • Glucose-6-Phosphatase