Exogenous corticosteroids and in utero oxygenation modulate indices of fetal insulin secretion.
Low birth weight has long-term effects on glucose-insulin homeostasis. Factors that could mediate intra-uterine "programing" of glucose homeostasis include endogenous and exogenous glucocorticoids, adipose tissue-secreted factors such as adiponectin, and in utero hypoxia. Here, we studied 123 fetuses with gestational age (GA) between 25 and 37 wk and birth weight sd score (BW SDS) between -2.79 and 2.42. We measured proinsulin, C-peptide, insulin, and adiponectin in umbilical vein (UV) plasma and calculated the proinsulin to insulin ratio as a measure of beta-cell secretory function. These indices were related to GA, BW SDS, time since the last maternal betamethasone administration, and blood gas data. Insulin and C-peptide were correlated with BW SDS but not GA, whereas the proinsulin to insulin ratio was inversely correlated with BW SDS. The proinsulin to insulin ratio was raised (P = 0.002) in fetuses with UV PO(2) less than or equal to 21.3 mm Hg (i.e. the 50th percentile) compared with those with PO(2) more than 21.3 mm Hg, inferring that in utero hypoxia engenders beta-cell secretory dysfunction. Proinsulin, insulin, and C-peptide were markedly but transiently (<24 h) elevated after maternal betamethasone administration, returning thereafter to concentrations measured in noncorticosteroid-treated fetuses. However, there was considerable variability within the less than 24-h betamethasone group: the indices of insulin secretion were related to UV PO(2), suggesting that hypoxia attenuates the responsiveness of fetal beta-cells to corticosteroids. Adiponectin was not related to any of the insulin indices. In conclusion, we have identified two environmental signals that modulate fetal insulin output: maternal corticosteroids produce a transient surge in fetal insulin synthesis and secretion, whereas in utero hypoxia disturbs the insulin secretory process.
Verhaeghe
Johan
J
Department of Obstetrics and Gynecology, U.Z. Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. johan.verhaeghe@uz.kuleuven.ac.be
van Bree
Rita
R
van Herck
Erik
E
Coopmans
Willy
W
D052242:Adiponectin; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D001623:Betamethasone / Q000494:pharmacology; D001724:Birth Weight; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011384:Proinsulin / Q000097:blood; D014471:Umbilical Veins
D052242:Adiponectin; D000305:Adrenal Cortex Hormones; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011384:Proinsulin; D001623:Betamethasone