Increased fetal insulin concentrations for one week fail to improve insulin secretion or [Beta]-cell mass in fetal sheep with chronically reduced glucose supply

Maternal undernutrition during pregnancy and placental insufficiency are characterized by impaired development of fetal pancreatic ...-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 un...

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Bibliographic Details
Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2013-01, Vol.304 (1), p.R50
Main Authors: Lavezzi, Jinny R, Thorn, Stephanie R, O'Meara, Meghan C, LoTurco, Dan, Brown, Laura D, Hay, William W, Rozance, Paul J
Format: Article
Language:English
Subjects:
Animal reproduction
Cells
Glucose
Insulin
Pancreas
Physiology
Sheep
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Summary:Maternal undernutrition during pregnancy and placental insufficiency are characterized by impaired development of fetal pancreatic ...-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 ...-cell defects. Therefore, we measured fetal insulin secretion and ...-cell mass following prolonged reduced fetal glucose supply in sheep. We also tested whether restoring physiological insulin concentrations would correct any ...-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. ...-Cell, pancreatic, and fetal mass were 50%, 37%, and 40% lower in HG compared with CON fetuses, respectively (P < 0.05). Insulin secretion and ...-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 ...-cell mass, and is not correctable with insulin. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0363-6119
1522-1490