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Communication dans un congrès

The spontaneously decreased beta cell mass and pancreatic IGF2 production in the GK fetal rat are both improved in response to maternal undernutrition

Abstract : The Goto-Kakizaki (GK) rat is a spontaneous model of type 2 diabetes with a defective beta-cell mass detectable in late fetal development (21.5 days postcoitum [dpc]) and the diminished IGF- 2 production seems to be involved in this effect. Since we have previously shown that early undernutrition increases beta-cell mass in foetuses at term, the aim of the present study was to investigate whether a condition of maternal malnutrition might similarly positively modulate the beta-cell mass in GK foetuses. In addition, the implication of the IGF system, which is highly responsive to nutritional status in these processes was evaluated. To this end, we have measured in 21.5 dpc undernourished GK foetuses (GK-U) 1) serum GH and IGF levels, 2) beta-cell mass, 3) replication and differentiation of beta-cells, and 4) IGF-1 and -2 protein content in liver and pancreas. All values were compared to those in control GK foetuses. GK rats were obtained from our colony of GK/Par rats. Pregnant GK females were food restricted (65% restriction) during the last week of gestation. Serum concentrations of GH, IGF-1 and -2 were measured by radioimmunoassay. Beta-cell mass, beta-cell differentiation and beta-cell replication were evaluated using quantitative immunohistochemistry methods. The protein content of IGF-1 and -2 was analyzed by western blot in pancreas and liver. Although in no case the GK-U values reached the levels of control Wistar rats, the results show that beta-cell mass increased by 90% in GK-U foetuses as compared to the GK group and that both beta-cell neogenesis and replication were stimulated as well. On the other hand, similar serum GH, IGF-1 and -2 levels were observed in GK and GK-U foetuses. Malnutrition affected IGF protein content in the various tissues studied. Particularly relevant was a 3-fold increase of pancreatic IGF-2 protein levels in GK-U foetuses. Our data suggest that 1) maternal malnutrition increased betacell mass and pancreatic IGF-2 protein levels in GK-U foetuses at 21.5 dpc, 2) the increased beta-cell mass could be related to the stimulation of both betacell neogenesis and beta-cell replication, 3) the locally increased pancreatic IGF-2 may be instrumental in these processes. They also illustrate for the first time that enhanced IGF-2 production in the pancreas can be triggered by a nutritional manipulation of the mother. So far it is not known whether or not undernutrition of the mother is sufficient to delay/decrease the risk of the GK/Par rat for developing overt hyperglycaemia at adult age.
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Déposant : Migration Prodinra <>
Soumis le : jeudi 4 juin 2020 - 03:08:31
Dernière modification le : vendredi 12 juin 2020 - 10:43:26


  • HAL Id : hal-02758135, version 1
  • PRODINRA : 366146
  • WOS : 000249395600500



E. Fernandez, M.N. Gangnereau, Sophie Calderari, L. de Miguel, P. Serradas, et al.. The spontaneously decreased beta cell mass and pancreatic IGF2 production in the GK fetal rat are both improved in response to maternal undernutrition. 43. Annual Meeting of The European of Association for the Study of Diabetes, European Association for the Study of Diabetes (EASD). GBR., Sep 2007, Amsterdam, Netherlands. 538 p. ⟨hal-02758135⟩



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