en
Scientific article
English

Pancreatic-specific inactivation of IGF-I gene causes enlarged pancreatic islets and significant resistance to diabetes

Published inDiabetes, vol. 53, no. 12, p. 3131-3141
Publication date2004
Abstract

The dogma that IGF-I stimulates pancreatic islet growth has been challenged by combinational targeting of IGF or IGF-IR (IGF receptor) genes as well as beta-cell-specific IGF-IR gene deficiency, which caused no defect in islet cell growth. To assess the physiological role of locally produced IGF-I, we have developed pancreatic-specific IGF-I gene deficiency (PID) by crossing Pdx1-Cre and IGF-I/loxP mice. PID mice are normal except for decreased blood glucose level and a 2.3-fold enlarged islet cell mass. When challenged with low doses of streptozotocin, control mice developed hyperglycemia after 6 days that was maintained at high levels for at least 2 months. In contrast, PID mice only exhibited marginal hyperglycemia after 12 days, maintained throughout the experiment. Fifteen days after streptozotocin, PID mice demonstrated significantly higher levels of insulin production. Furthermore, streptozotocin-induced beta-cell apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL] assay) was significantly prevented in PID mice. Finally, PID mice exhibited a delayed onset of type 2 diabetes induced by a high-fat diet, accompanied by super enlarged pancreatic islets, increased insulin mRNA levels, and preserved sensitivity to insulin. Our results suggest that locally produced IGF-I within the pancreas inhibits islet cell growth; its deficiency provides a protective environment to the beta-cells and potential in combating diabetes.

Keywords
  • Animals
  • Apoptosis
  • Blood Glucose/metabolism
  • Female
  • Gene Silencing/ physiology
  • Glucagon/blood
  • Glucose Tolerance Test
  • Immunity, Innate/genetics
  • Insulin/blood
  • Insulin-Like Growth Factor I/ deficiency/ genetics
  • Islets of Langerhans/ cytology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Mice, Knockout
  • Pancreas/ physiology
Citation (ISO format)
LU, Yarong et al. Pancreatic-specific inactivation of IGF-I gene causes enlarged pancreatic islets and significant resistance to diabetes. In: Diabetes, 2004, vol. 53, n° 12, p. 3131–3141. doi: 10.2337/diabetes.53.12.3131
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ISSN of the journal0012-1797
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