Regulation of pancreatic beta cell mass by neuronal signals from the liver

Science. 2008 Nov 21;322(5905):1250-4. doi: 10.1126/science.1163971.


Metabolic regulation in mammals requires communication between multiple organs and tissues. The rise in the incidence of obesity and associated metabolic disorders, including type 2 diabetes, has renewed interest in interorgan communication. We used mouse models to explore the mechanism whereby obesity enhances pancreatic beta cell mass, pathophysiological compensation for insulin resistance. We found that hepatic activation of extracellular regulated kinase (ERK) signaling induced pancreatic beta cell proliferation through a neuronal-mediated relay of metabolic signals. This metabolic relay from the liver to the pancreas is involved in obesity-induced islet expansion. In mouse models of insulin-deficient diabetes, liver-selective activation of ERK signaling increased beta cell mass and normalized serum glucose levels. Thus, interorgan metabolic relay systems may serve as valuable targets in regenerative treatments for diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Central Nervous System / metabolism
  • Diabetes Mellitus, Experimental / metabolism
  • Hyperplasia
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Liver / metabolism*
  • MAP Kinase Kinase 1 / metabolism*
  • MAP Kinase Signaling System*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Obesity / metabolism*
  • Pancreas / innervation
  • Recombinant Proteins / metabolism
  • Vagus Nerve / cytology
  • Vagus Nerve / metabolism
  • Xenopus


  • Insulin
  • Recombinant Proteins
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse