Affiliation:
1. Perinatal Research Center, Section of Neonatology, Department of Pediatrics,
2. Center for Women's Health Research, University of Colorado Denver School of Medicine, Aurora, Colorado
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.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
8 articles.
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