title: Differential effects of chronic pulsatile versus chronic constant maternal hyperglycemia on fetal pancreatic β-cells.
abstract: 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.
authors.affiliation: Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Mackenzie S
authors.initials: MS
authors.lastname: Frost
authors.forename: Aqib H
authors.initials: AH
authors.lastname: Zehri
authors.forename: Sean W
authors.initials: SW
authors.lastname: Limesand
authors.forename: William W
authors.initials: WW
authors.lastname: Hay
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rozance
mesh_terms: D000818:Animals; D017209:Apoptosis; D002908:Chronic Disease; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006965:Hyperplasia / Q000209:etiology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D008297:Male; D008938:Mitosis; D010179:Pancreas / Q000166:cytology / Q000196:embryology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011897:Random Allocation; D012756:Sheep
chemical_list: D007328:Insulin