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Instituto de Bioquímica, Consejo Superior de Investigaciones Cientificas Universidad Complutense de Madrid (M.A.M., S.R., E.F., L.G., A.M.P.-L., F.E., C.A.), Facultad de Farmacia, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain; and the Laboratory of Physiopathology of Nutrition (P.S., M.N.G., M.L., B.P.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 7059, Université Paris 7/D, Denis Diderot, 7525 Paris Cedex 05, France
Address all correspondence and requests for reprints to: Dr. Carmen Alvarez, Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain. E-mail: calvarez{at}farm.ucm.es.
We have previously shown that fetuses from protein-caloric undernourished pregnant rats (35% of control diet during the last week of pregnancy) at 21.5 d post coitum exhibit increased ß-cell mass. This alteration is correlated with increased insulinemia and total pancreatic insulin content, a pattern similar to that reported in infants of mild diabetic mothers. In this work, we investigated in undernourished fetuses: 1) whether availability of growth factors such as insulin, GH, and IGFs and their binding proteins (IGFBPs) could be implicated in this alteration, and 2) the ß-cell mitogenic response to IGFs in vitro. The results show that maternal undernutrition increases pancreatic IGF-I expression and islet IGF-I receptor content in undernourished fetuses, whereas hepatic IGF-I expression and serum IGF-I levels were decreased. No changes were observed in serum IGF-II, and its expression was diminished in undernourished pancreases and unchanged in the liver, compared with control fetuses. Serum levels and liver and pancreatic mRNA expression of IGFBP-1 were found to be normal in undernourished fetuses, whereas the serum concentration and abundance of IGFBP-2 mRNA in pancreas were increased. Finally, the ß-cell mitogenic response to IGFs in vitro was significantly increased in undernourished fetal islets, compared with controls. In conclusion, in undernourished fetuses the increased ß-cell mass can be related to the stimulation of replicative ß-cell response due to locally increased pancreatic IGF-I mRNA; this effect is perhaps potentiated or favored by the enhanced islet IGF-I receptor content and pancreatic IGFBP-2 gene expression.
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E. Fernandez, M. A. Martin, S. Fajardo, D. Bailbe, M. N. Gangnerau, B. Portha, F. Escriva, P. Serradas, and C. Alvarez Undernutrition does not alter the activation of beta-cell neogenesis and replication in adult rats after partial pancreatectomy Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E913 - E921. [Abstract] [Full Text] [PDF] |
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