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J Endocrinol. 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.

Author information

1
Departments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USA.
2
Departments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USADepartments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USADepartments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USA.
3
Departments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USADepartments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USADepartments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USA pvuguin@nshs.edu maureen.charron@einstein.yu.edu.
4
Departments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USADepartments of PediatricsNeonatologyBiochemistryObstetrics and Gynecology and Women's HealthMedicineAlbert Einstein College of Medicine, 1300 Morris Park Avenue, F312, Bronx, New York 10461, USADepartment of PediatricsHofstra School of Medicine, Cohen Children's Medical Center, 1991 Marcus Avenue, Lake Success, New York 11402, USA pvuguin@nshs.edu maureen.charron@einstein.yu.edu.

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

PMID:
24895417
PMCID:
PMC4287255
DOI:
10.1530/JOE-14-0114
[Indexed for MEDLINE]
Free PMC Article
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