Undernutrition of the GK rat during gestation improves pancreatic IGF-2 and beta-cell mass in the fetuses

Abstract

The Goto–Kakizaki (GK) rat is a type 2 diabetes model with a defective beta-cell mass detectable in late fetal development. Diminished IGF-2 production seems to be involved in this effect. Herein, we analyzed the effect of maternal food-restriction on the beta-cell mass of GK fetuses and the involvement of the IGF system, highly responsive to nutritional status in this process. To this end, in undernourished GK fetuses (U-GK), we measured serum GH/IGF levels, beta-cell mass, replication and differentiation, and IGF-1/-2 protein content in liver and pancreas tissue. Pregnant GK females were food restricted (65% restriction) during the last week of gestation. Our results show that maternal malnutrition ameliorates beta-cell mass in U-GK fetuses and a specific pancreatic IGF-2 increase may be instrumental in this effect. Further studies are needed to determine whether maternal undernutrition is sufficient to delay or decrease the risk of the GK rat for developing diabetes.

Keywords::

• Undernutrition
• GK rats
• IGF
• beta-cell
• replication
• neogenesis

Acknowledgements

This work was supported by several grants: BFU2005-02849, BFU2008-02930 from the Ministerio de Educación y Ciencia and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) which is an ISCIII Project (Spain), the Centre National de la Recherche Scientifique, the French ANR (programme Physio 2006-Prograbeta), the NEB Research Foundation and the French/Spain PICASSO Program /Acción Integrada Ref. HF2007-0076.E. Fernández-Millán is a recipient from CIBERDEM.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.