Effects of genetics and In utero diet on murine pancreatic development

Chia Lei Lin, Lyda Williams, Yoshinori Seki, Harpreet Kaur, Kirsten Hartil, Ariana Fiallo, A. Scott Glenn, Ellen B. Katz, Maureen J. Charron, Patricia M. Vuguin

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)217-227
Number of pages11
JournalJournal of Endocrinology
Volume222
Issue number2
DOIs
StatePublished - 2014

Keywords

  • Fetus
  • Glucagon cells
  • High-fat diet
  • Pancreas
  • Programing

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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  • Cite this

    Lin, C. L., Williams, L., Seki, Y., Kaur, H., Hartil, K., Fiallo, A., Glenn, A. S., Katz, E. B., Charron, M. J., & Vuguin, P. M. (2014). Effects of genetics and In utero diet on murine pancreatic development. Journal of Endocrinology, 222(2), 217-227. https://doi.org/10.1530/JOE-14-0114