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. 2014 Aug;222(2):217-27.
doi: 10.1530/JOE-14-0114. Epub 2014 Jun 3.

Effects of genetics and in utero diet on murine pancreatic development

Chia-Lei Lin  1 , Lyda Williams  1 , Yoshinori Seki  1 , Harpreet Kaur  2 , Kirsten Hartil  1 , Ariana Fiallo  1 , A Scott Glenn  1 , Ellen B Katz  1 , Maureen J Charron  3 , Patricia M Vuguin  4
Affiliations

Effects of genetics and in utero diet on murine pancreatic development

Chia-Lei Lin et al. J Endocrinol. 2014 Aug.

Abstract

Intrauterine (IU) malnutrition could alter pancreatic development. In this study, we describe the effects of high-fat diet (HFD) during pregnancy on fetal growth and pancreatic morphology in an 'at risk' animal model of metabolic disease, the glucose transporter 4 (GLUT4) heterozygous mouse (G4+/-). WT female mice mated with G4+/- males were fed HFD or control diet (CD) for 2 weeks before mating and throughout pregnancy. At embryonic day 18.5, fetuses were killed and pancreata isolated for analysis of morphology and expression of genes involved in insulin (INS) cell development, proliferation, apoptosis, glucose transport and function. Compared with WT CD, WT HFD fetal pancreata had a 2.4-fold increase in the number of glucagon (GLU) cells (P=0.023). HFD also increased GLU cell size by 18% in WT pancreata compared with WT CD. Compared with WT CD, G4+/- CD had an increased number of INS cells and decreased INS and GLU cell size. Compared with G4+/- CD, G4+/- HFD fetuses had increased pancreatic gene expression of Igf2, a mitogen and inhibitor of apoptosis. The expression of genes involved in proliferation, apoptosis, glucose transport, and INS secretion was not altered in WT HFD compared with G4+/- HFD pancreata. In contrast to WT HFD pancreata, HFD exposure did not alter pancreatic islet morphology in fetuses with GLUT4 haploinsufficiency; this may be mediated in part by increased Igf2 expression. Thus, interactions between IU diet and fetal genetics may play a critical role in the developmental origins of health and disease.

Keywords: fetus; glucagon cells; high-fat diet; pancreas; programing.

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Conflict of interest statement

Declaration of Interest:

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1
Figure 1
Photomicrographs of confocal images of representative islets from embryos at e-18.5 immunostained for insulin (green) (A–D), glucagon (red) (A–D), and insulin (red) (E–H) and Pdx1 (green) (E–H) cells in WT C (A, E), WT HFD (B, F), G4+/− CD (C, G) and G4+/− HFD (D, H). Pancreata from WT HFD (B) fetuses exhibit an increased number of GLU cells (red) as compared to WT CD (A), G4+/− CD (C) and G4+/− HFD (D) fetuses. HFD did not alter the expression or the localization of Pdx1 (green) in WT (E, F) or G4+/− (G, H) fetal pancreata compared to those from CD pancreata. Scale = 40 μm
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