title: Glucocorticoid-Induced Preterm Birth and Neonatal Hyperglycemia Alter Ovine β-Cell Development.
abstract: Adults born preterm are at increased risk of impaired glucose tolerance and diabetes. Late gestation fetuses exposed to high blood glucose concentration also are at increased risk of impaired glucose tolerance as adults. Preterm babies commonly become hyperglycemic and are thus exposed to high blood glucose concentration at an equivalent stage of pancreatic maturation. It is not known whether preterm birth itself, or complications of prematurity, such as hyperglycemia, alter later pancreatic function. To distinguish these, we made singleton preterm lambs hyperglycemic (HYPER) for 12 days after birth with a dextrose infusion and compared them with vehicle-treated preterm and term controls and with HYPER lambs made normoglycemic with an insulin infusion. Preterm birth reduced β-cell mass, apparent by 4 weeks after term and persisting to adulthood (12 mo), and was associated with reduced insulin secretion at 4 months (juvenile) and reduced insulin mRNA expression in adulthood. Hyperglycemia in preterm lambs further down-regulated key pancreatic gene expression in adulthood. These findings indicate that reduced β-cell mass after preterm birth may be an important factor in increased risk of diabetes after preterm birth and may be exacerbated by postnatal hyperglycemia.
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Amita
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Frank H
authors.initials: FH
authors.lastname: Bloomfield
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Connor
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Mike
authors.initials: M
authors.lastname: Dragunow
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Thorstensen
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Oliver
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Sloboda
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Harding
authors.affiliation: Liggins Institute (A.B., F.H.B., K.L.C., E.B.T., M.H.O., D.M.S., J.E.H., J.M.A.), Department of Paediatrics: Child and Youth Health (F.H.B., J.M.A.), Faculty of Medical and Health Sciences, and Centre of Brain Research (M.D.), Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand; and Gravida: National Centre for Growth and Development (A.B., F.H.B., K.L.C., M.D., M.H.O., D.M.S.), Auckland 1023, New Zealand.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Alsweiler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D015870:Gene Expression; D005938:Glucocorticoids; D005947:Glucose; D006943:Hyperglycemia / Q000139:chemically induced / Q000662:veterinary*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D047928:Premature Birth / Q000139:chemically induced / Q000662:veterinary*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D012757:Sheep Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005947:Glucose