6-ketoprostaglandin-f1-alpha and Hyperinsulinism

The response of renal hemodynamics and sodium excretion (NaU) to an infusion of L-arginine, in the presence (experiment I) or absence (experiment II) of endogenous insulin secretion and during a sustained hyperinsulinemic euglycemic state (experiment III), was studied in 10 age-matched beagle dogs. The experiments were preceded by a standard oral glucose tolerance test (OGTT), performed 1 week before experiment I. One week resting periods were allowed between experiments I, II, and III. No differences in renal hemodynamics and NaU were observed between basal (experiment I) and insulin secretion suppressed states (experiment II). L-Arginine infusion increased renal plasma flow (RPF), glomerular filtration rate (GFR), and NaU to a similar extent in both experiments. The hyperinsulinemic-euglycemic state (experiment III) induced a decrease in renal hemodynamics and NaU. In this situation, the infusion of L-arginine increased NaU, but was unable to increase RPF and GFR. Our data suggest that a sustained hyperinsulinemic state can interact with the physiological vasoactive mechanisms involved in the regulation of renal vasculature. These results may be pertinent to human disease, especially in pathological conditions in which insulin resistance is present.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arginine; Blood Glucose; Cyclic GMP; Dogs; Glomerular Filtration Rate; Glucose Tolerance Test; Hyperinsulinism; Infusions, Intravenous; Insulin; Renal Circulation; Renal Plasma Flow; Sodium

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.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Chronic Disease; Female; Fetal Diseases; Hyperinsulinism; Insulin; Pregnancy; Prostaglandins; Sheep; Thromboxane B2