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Fetal insulin-like growth factor-2 production is impaired in the GK rat model of type 2 diabetes.
Serradas, Patricia; Goya, Luis; Lacorne, Matthieu; Gangnerau, Marie-Noëlle; Ramos, Sonia; Alvarez, Carmen; Pascual-Leone, Ana-Maria; Portha, Bernard.
Afiliação
  • Serradas P; Laboratory of Physiopathology of Nutrition, Université Paris, Paris, France. serradas@paris7.jussieu.fr
Diabetes ; 51(2): 392-7, 2002 Feb.
Article em En | MEDLINE | ID: mdl-11812746
ABSTRACT
At late fetal age (21.5 days postcoitum [dpc]), GK rats present a severely reduced beta-cell mass compared with Wistar rats. This anomaly largely antedates the onset of hyperglycemia in GK rats. Thus, the beta-cell mass deficit could represent the primary defect leading to type 2 diabetes in the adult. The aim of this work was to investigate, in GK fetuses at the end of fetal age (21.5 dpc), whether impaired availability of growth factors such as insulin, growth hormone, and IGFs and their IGF binding proteins (IGFBPs) could be instrumental in this anomaly. Although it confirms that GK fetuses are hypoinsulinemic despite enhanced plasma glucose level due to maternal hyperglycemia, the present study shows for the first time that IGF-2 expression in the liver and pancreas and IGF-2 serum levels are decreased in GK fetuses. Serum level as well as liver and pancreatic mRNA expression of IGFBP-2 were found to be normal in GK fetuses, whereas serum level and liver mRNA expression of IGFBP-1 were increased. Finally, we found that the maximal beta-cell mitogenic response to IGFs in vitro is kept intact, therefore suggesting that the direct biological action of IGFs on fetal GK beta-cells is not grossly impaired. In conclusion, in GK fetuses at 21.5 dpc, the defective IGF-2 production appears to be an early landmark in the pathological sequence leading to retardation of beta-cell growth in the fetal GK rat.
Assuntos
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Base de dados: MEDLINE Assunto principal: Fator de Crescimento Insulin-Like II / Diabetes Mellitus Tipo 2 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Diabetes Ano de publicação: 2002 Tipo de documento: Article País de afiliação: França
Buscar no Google
Base de dados: MEDLINE Assunto principal: Fator de Crescimento Insulin-Like II / Diabetes Mellitus Tipo 2 Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Diabetes Ano de publicação: 2002 Tipo de documento: Article País de afiliação: França