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Journal of Pregnancy
Volume 2012 (2012), Article ID 812094, 8 pages
Research Article

Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells

1Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USA
2Department of Animal Sciences, University of Arizona, Tucson, AZ 85719, USA
3Department of Pediatrics, UCD Perinatal Research Center, University of Colorado School of Medicine, 13243 East 23rd Avenue, MS F441, Aurora, CO 80045, USA

Received 6 August 2012; Accepted 2 October 2012

Academic Editor: Leena Hilakivi-Clarke

Copyright © 2012 Mackenzie S. Frost et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Constant maternal hyperglycemia limits, while pulsatile maternal hyperglycemia may enhance, fetal glucose-stimulated insulin secretion (GSIS) in sheep. However, the impact of such different patterns of hyperglycemia on the development of the fetal β-cell is unknown. We measured the impact of one week of chronic constant hyperglycemia (CHG, ) versus pulsatile hyperglycemia (PHG, ) versus controls ( ) on the percentage of the fetal pancreas staining for insulin (β-cell area), mitotic and apoptotic indices and size of fetal β-cells, and fetal insulin secretion in sheep. Baseline insulin concentrations were higher in CHG fetuses ( ) compared to controls and PHG. GSIS was lower in the CHG group ( ) compared to controls and PHG. PHG β-cell area was increased 50% ( ) compared to controls and CHG. CHG β-cell apoptosis was increased over 400% ( ) compared to controls and PHG. These results indicate that late gestation constant maternal hyperglycemia leads to significant β-cell toxicity (increased apoptosis and decreased GSIS). Furthermore, pulsatile maternal hyperglycemia increases pancreatic β-cell area but did not increase GSIS, indicating decreased β-cell responsiveness. These findings demonstrate differential effects that the pattern of maternal hyperglycemia has on fetal pancreatic β-cell development, which might contribute to later life limitation in insulin secretion.