Regulation of pancreatic beta-cell mass and proliferation by SOCS-3

J Mol Endocrinol. 2005 Oct;35(2):231-43. doi: 10.1677/jme.1.01840.


Growth hormone and prolactin are important growth factors for pancreatic beta-cells. The effects exerted by these hormones on proliferation and on insulin synthesis and secretion in beta-cells are largely mediated through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Suppressors of cytokine signaling (SOCS) proteins are specific inhibitors of the JAK/STAT pathway acting through a negative-feedback loop. To investigate in vivo effects of SOCS-3 in growth hormone (GH)/prolactin signaling in beta-cells we generated transgenic mice with beta-cell-specific overexpression of SOCS-3. The relative beta-cell proliferation and volume in the mice were measured by morphometry. Beta-cell volume of transgenic female mice was reduced by over 30% compared with beta-cell volume in wild-type female mice. Stimulation of transgenic islets in vitro with GH showed a reduced tyrosine phosphorylation of STAT-5 when compared with wild-type islets. Transduction of primary islet cultures with adenoviruses expressing various SOCS proteins followed by stimulation with GH or glucagon-like peptide-1 (GLP-1) revealed that SOCS-3 inhibited GH- but not GLP-1-mediated islet cell proliferation, indicating that the decreased beta-cell volume observed in female transgenic mice could be caused by an inhibition of GH-induced beta-cell proliferation by SOCS-3. In spite of the reduced beta-cell volume the transgenic female mice exhibited enhanced glucose tolerance compared with wild-type littermates following an oral glucose-tolerance test. Together these data suggest that SOCS-3 modulates cytokine signaling in pancreatic beta-cells and therefore potentially could be a candidate target for development of new treatment strategies for diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Cell Proliferation*
  • Female
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose Tolerance Test
  • Growth Hormone / metabolism
  • In Situ Hybridization
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / physiology*
  • Janus Kinase 1
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Protein-Tyrosine Kinases / metabolism
  • Random Allocation
  • Rats
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction / physiology
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Transgenes


  • Blood Glucose
  • Insulin
  • STAT5 Transcription Factor
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Glucagon-Like Peptide 1
  • Growth Hormone
  • Protein-Tyrosine Kinases
  • Jak1 protein, mouse
  • Jak1 protein, rat
  • Janus Kinase 1