Does IGF-I stimulate pancreatic islet cell growth?
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 beta-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 beta-cell-specific inactivation of IGF-IR gene causes no change in beta-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 beta-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 beta-cell loss.
Liu
Jun-Li
JL
Department of Medicine, McGill University Health Centre, Montreal, QC, Canada. jun-li.liu@mcgill.ca
D000818:Animals; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1