Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells
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 wee...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Journal of Pregnancy |
| Online Access: | http://dx.doi.org/10.1155/2012/812094 |
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| author | Mackenzie S. Frost Aqib H. Zehri Sean W. Limesand William W. Hay Paul J. Rozance |
| author_facet | Mackenzie S. Frost Aqib H. Zehri Sean W. Limesand William W. Hay Paul J. Rozance |
| author_sort | Mackenzie S. Frost |
| collection | DOAJ |
| description | 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, n=6) versus pulsatile hyperglycemia (PHG, n=5) versus controls (n=7) 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 (P<0.05) compared to controls and PHG. GSIS was lower in the CHG group (P<0.005) compared to controls and PHG. PHG β-cell area was increased 50% (P<0.05) compared to controls and CHG. CHG β-cell apoptosis was increased over 400% (P<0.05) 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. |
| format | Article |
| id | doaj-art-c2d9a137a2be426f9a45010d598c3673 |
| institution | Kabale University |
| issn | 2090-2727 2090-2735 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
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| series | Journal of Pregnancy |
| spelling | doaj-art-c2d9a137a2be426f9a45010d598c36732025-02-03T06:14:17ZengWileyJournal of Pregnancy2090-27272090-27352012-01-01201210.1155/2012/812094812094Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-CellsMackenzie S. Frost0Aqib H. Zehri1Sean W. Limesand2William W. Hay3Paul J. Rozance4Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USADepartment of Animal Sciences, University of Arizona, Tucson, AZ 85719, USADepartment of Animal Sciences, University of Arizona, Tucson, AZ 85719, USADepartment of Pediatrics, UCD Perinatal Research Center, University of Colorado School of Medicine, 13243 East 23rd Avenue, MS F441, Aurora, CO 80045, USADepartment of Pediatrics, UCD Perinatal Research Center, University of Colorado School of Medicine, 13243 East 23rd Avenue, MS F441, Aurora, CO 80045, USAConstant 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, n=6) versus pulsatile hyperglycemia (PHG, n=5) versus controls (n=7) 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 (P<0.05) compared to controls and PHG. GSIS was lower in the CHG group (P<0.005) compared to controls and PHG. PHG β-cell area was increased 50% (P<0.05) compared to controls and CHG. CHG β-cell apoptosis was increased over 400% (P<0.05) 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.http://dx.doi.org/10.1155/2012/812094 |
| spellingShingle | Mackenzie S. Frost Aqib H. Zehri Sean W. Limesand William W. Hay Paul J. Rozance Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells Journal of Pregnancy |
| title | Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells |
| title_full | Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells |
| title_fullStr | Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells |
| title_full_unstemmed | Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells |
| title_short | Differential Effects of Chronic Pulsatile versus Chronic Constant Maternal Hyperglycemia on Fetal Pancreatic β-Cells |
| title_sort | differential effects of chronic pulsatile versus chronic constant maternal hyperglycemia on fetal pancreatic β cells |
| url | http://dx.doi.org/10.1155/2012/812094 |
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