Differential effects of chronic pulsatile versus chronic constant maternal hyperglycemia on fetal pancreatic β-cells

Mackenzie S. Frost, Aqib H. Zehri, Sean W. Limesand, William W. Hay, Paul J. Rozance

Research output: Contribution to journalArticle

6 Scopus citations

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 (P0.05) 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.

Original languageEnglish (US)
Article number812094
JournalJournal of Pregnancy
Volume2012
DOIs
StatePublished - Nov 19 2012

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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