Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor

J Clin Invest. 2002 Oct;110(7):1011-9. doi: 10.1172/JCI15276.


Defective insulin secretion is a feature of type 2 diabetes that results from inadequate compensatory increase of beta cell mass and impaired glucose-dependent insulin release. beta cell proliferation and secretion are thought to be regulated by signaling through receptor tyrosine kinases. In this regard, we sought to examine the potential proliferative and/or antiapoptotic role of IGFs in beta cells by tissue-specific conditional mutagenesis ablating type 1 IGF receptor (IGF1R) signaling. Unexpectedly, lack of functional IGF1R did not affect beta cell mass, but resulted in age-dependent impairment of glucose tolerance, associated with a decrease of glucose- and arginine-dependent insulin release. These observations reveal a requirement of IGF1R-mediated signaling for insulin secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exocytosis
  • Glucose Transporter Type 2
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Mice
  • Monosaccharide Transport Proteins / analysis
  • Phenotype
  • RNA, Messenger / analysis
  • Receptor, IGF Type 1 / deficiency
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / physiology*


  • Glucose Transporter Type 2
  • Insulin
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Receptor, IGF Type 1