title: Increased fetal insulin concentrations for one week fail to improve insulin secretion or β-cell mass in fetal sheep with chronically reduced glucose supply.
abstract: Maternal undernutrition during pregnancy and placental insufficiency are characterized by impaired development of fetal pancreatic β-cells. Prolonged reduced glucose supply to the fetus is a feature of both. It is unknown if reduced glucose supply, independent of other complications of maternal undernutrition and placental insufficiency, would cause similar β-cell defects. Therefore, we measured fetal insulin secretion and β-cell mass following prolonged reduced fetal glucose supply in sheep. We also tested whether restoring physiological insulin concentrations would correct any β-cell defects. Pregnant sheep received either a direct saline infusion (CON = control, n = 5) or an insulin infusion (HG = hypoglycemic, n = 5) for 8 wk in late gestation (75 to 134 days) to decrease maternal glucose concentrations and reduce fetal glucose supply. A separate group of HG fetuses also received a direct fetal insulin infusion for the final week of the study with a dextrose infusion to prevent a further fall in glucose concentration [hypoglycemic + insulin (HG+I), n = 4]. Maximum glucose-stimulated insulin concentrations were 45% lower in HG fetuses compared with CON fetuses. β-Cell, pancreatic, and fetal mass were 50%, 37%, and 40% lower in HG compared with CON fetuses, respectively (P < 0.05). Insulin secretion and β-cell mass did not improve in the HG+I fetuses. These results indicate that chronically reduced fetal glucose supply is sufficient to reduce pancreatic insulin secretion in response to glucose, primarily due to reduced pancreatic and β-cell mass, and is not correctable with insulin.
authors.affiliation: Perinatal Research Center, Section of Neonatology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, USA.
authors.forename: Jinny R
authors.initials: JR
authors.lastname: Lavezzi
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Thorn
authors.forename: Meghan C
authors.initials: MC
authors.lastname: O'Meara
authors.forename: Dan
authors.initials: D
authors.lastname: LoTurco
authors.forename: Laura D
authors.initials: LD
authors.lastname: Brown
authors.forename: William W
authors.initials: WW
authors.lastname: Hay
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rozance
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D006946:Hyperinsulinism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D044342:Malnutrition / Q000097:blood / Q000503:physiopathology*; D011247:Pregnancy; D012756:Sheep / Q000097:blood / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin