title: Effects of genetics and in utero diet on murine pancreatic development.
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.
authors.affiliation: 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.
authors.forename: Chia-Lei
authors.initials: CL
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Lyda
authors.initials: L
authors.lastname: Williams
authors.affiliation: 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.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Seki
authors.affiliation: 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.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.affiliation: 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.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hartil
authors.affiliation: 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.
authors.forename: Ariana
authors.initials: A
authors.lastname: Fiallo
authors.affiliation: 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.
authors.forename: A Scott
authors.initials: AS
authors.lastname: Glenn
authors.affiliation: 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.
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Katz
authors.affiliation: 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.
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.affiliation: 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.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Vuguin
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D005934:Glucagon / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D051379:Mice; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D007335:Insulin-Like Growth Factor II; D005934:Glucagon
keywords: fetus; glucagon cells; high-fat diet; pancreas; programing