Cell Biochemistry and Biophysics

, Volume 48, Issue 2–3, pp 115–125 | Cite as

Does IGF-I stimulate pancreatic islet cell growth?

  • Jun-Li LiuEmail author
Original Paper


Both IGF-I and its receptor (IGF-IR) are specifically expressed in various cell types of the endocrine pancreas. IGF-I has long been considered a growth factor for islet cells as it induces DNA synthesis in a glucose-dependent manner, prevents Fas-mediated autoimmune β-cell destruction and delays onset of diabetes in non-obese diabetic (NOD) mice. Islet-specific IGF-I overexpression promotes islet cell regeneration in diabetic mice. However, in the last few years, results from most gene-targeted mice have challenged this view. For instance, combined inactivation of insulin receptor and IGF-IR or IGF-I and IGF-II genes in early embryos results in no defect on islet cell development; islet β-cell-specific inactivation of IGF-IR gene causes no change in β-cell mass; liver- and pancreatic-specific IGF-I gene deficiency (LID and PID mice) suggests that IGF-I exerts an inhibitory effect on islet cell growth albeit indirectly through controlling growth hormone release or expression of Reg family genes. These results need to be evaluated with potential gene redundancy, model limitations, indirect effects and ligand-receptor cross-activations within the insulin/IGF family. Although IGF-I causes islet β-cell proliferation and neogenesis directly, what occur in normal physiology, pathophysiology or during development of an organism might be different. Locally produced and systemic IGF-I does not seem to play a positive role in islet cell growth. Rather, it is probably a negative regulator through controlling growth hormone and insulin release, hyperglycemia, or Reg gene expression. These results complicate the perspective of an IGF-I therapy for β-cell loss.


Reg family proteins Insulin Tissue-specific gene targeting IGF-I receptor Islet β-cells Growth Secretion Apoptosis Overexpression Diabetes. 



This work was supported by a Career Development Award (2–2000–507) from the Juvenile Diabetes Research Foundation International, New York, NY, operating grants (MOP-53206, NMD-83124) from Canadian Institutes of Health Research, John R. & Clara M. Fraser Memorial fund, and the Shanghai Education Commission (China). Research contributions were made by Y. Lu, K. Roberston, Y. Guo, R. Yu, Z. Tang, and Y. Liu of McGill University.


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Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Fraser Laboratories for Diabetes Research, Department of MedicineMcGill University Health CentreMontrealCanada
  2. 2.Endocrine and Metabolic DivisionE-Institutes of Shanghai Universities, Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghaiChina

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