Effects of chronic fetal hyperinsulinemia on plasma arachidonic acid and prostaglandin concentrations.
In adult diabetic subjects and infants of diabetic mothers, hyperglycemia has been associated with increased intravascular thromboxane and decreased prostacyclin production. Because of the association between states of altered insulin concentration and prostaglandin metabolism, we hypothesized that chronic experimentally induced fetal hyperinsulinemia results in perturbations in fetal arachidonic acid and prostaglandin metabolism. Arachidonic acid, thromboxane B2 (the stable breakdown product of thromboxane A2), and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin) were determined in the arterial blood of chronically catheterized fetal sheep after 9 to 12 days of continuous insulin (15 U.day-1, n = 7) or placebo (n = 5) infusion. Fetal insulin infusion resulted in fetal hypoglycemia and a reduction in fetal arterial plasma arachidonic acid concentration (p less than 0.01). In addition, the concentration of thromboxane B2 relative to 6-keto-prostaglandin F1 alpha was significantly reduced in the insulin-treated group compared with the placebo-treated group (p less than 0.03). We conclude that fetal hyperinsulinemia in sheep produces perturbations in prostaglandin metabolism with reductions in the plasma arachidonic acid concentration and in the plasma concentration of thromboxane A2 relative to prostacyclin. The hyperinsulinemic-hypoglycemic state in the fetus influences the relative proportion of the vasoconstricting to the vasodilating prostaglandins, thereby potentially modulating fetal vasomotor tone.
Stonestreet
B S
BS
Department of Pediatrics, Women and Infants' Hospital of Rhode Island 02905-2401.
Ogburn
P L
PL
Goldstein
M
M
Oh
W
W
Widness
J A
JA
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001095:Arachidonic Acids / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D005315:Fetal Diseases / Q000097:blood* / Q000139:chemically induced; D006946:Hyperinsulinism / Q000097:blood* / Q000139:chemically induced; D007328:Insulin / Q000494:pharmacology; D011247:Pregnancy; D011453:Prostaglandins / Q000097:blood*; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D007328:Insulin; D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha