title: Intermittent umbilical cord occlusion in the ovine fetus: effects on blood glucose, insulin, and glucagon and on pancreatic development.
abstract: OBJECTIVE
  To determine whether repetitive umbilical cord occlusion resulting in fetal hypoxemia but not cumulative acidosis also affects fetal glucose levels and the levels of the regulatory hormones insulin and glucagon, by altering glucose delivery and with repetitive insults by inducing fetal glucose production, thus possibly affecting pancreatic development.
  
  
  METHODS
  Fifteen chronically catheterized fetal sheep were studied over 21 days. Umbilical cord occlusions (UCOs) (duration 90 seconds) were performed every 30 minutes for 3-4 hours each day. Fetal arterial blood was sampled at predetermined times on days 1, 9, and 18 for blood gases, pH, glucose, lactate, insulin, and glucagon. When animals were sacrificed, fetal pancreatic tissues were collected for insulin immunostaining.
  
  
  RESULTS
  Blood glucose decreased acutely with each UCO but showed a cumulative increase of approximately 30% over the course of each sampling day. Although plasma insulin levels also increased over the course of sampling on days 9 and 18, plasma glucagon levels remained unchanged throughout the study. The percentage of pancreatic islet cells immunopositive for insulin, which averaged 67%, was also unchanged in experimental compared with control animals.
  
  
  CONCLUSIONS
  Umbilical cord occlusion during the latter part of pregnancy, which caused severe but limited hypoxemia, also resulted in acute decreases in blood glucose levels because of reduced exogenous glucose delivery and a cumulative increase in glucose in response to repetitive insults, possibly by inducing fetal glucose production, enhancing glucose delivery, or both. However, repetitive UCO as studied had minimal effect on plasma insulin levels and no effect on glucagon levels or on pancreatic immunostaining for insulin, and thus had no evident effect on pancreatic development.
authors.affiliation: CIHR Group in Fetal and Neonatal Health and Development, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Czikk
authors.forename: L R
authors.initials: LR
authors.lastname: Green
authors.forename: Y
authors.initials: Y
authors.lastname: Kawagoe
authors.forename: T J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: D J
authors.initials: DJ
authors.lastname: Hill
authors.forename: B S
authors.initials: BS
authors.lastname: Richardson
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D003250:Constriction; D005312:Fetal Blood / Q000737:chemistry*; D005934:Glucagon / Q000097:blood*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis / Q000097:blood*; D019344:Lactic Acid / Q000032:analysis; D010179:Pancreas / Q000737:chemistry / Q000196:embryology*; D012756:Sheep; D014470:Umbilical Cord / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019344:Lactic Acid; D005934:Glucagon