Production of 6-Oxo-Prostaglandin F_1α by Rat Aorta: Influence of Diabetes, Insulin Treatment, and Caloric Deprivation

Abstract

The production of 6-oxo-prostaglandin F_1α (6-oxo-PGF_1α), a stable metabolite of prostacyclin (PGI₂), was examined in three separate series of experiments in aortae from rats with diabetes induced by streptozotocin (SZ) and aortae from nondiabetic control rats.

In the first series, it was shown that production of 6-oxo-PGF_1α by aortae from rats with diabetes of 4–6-wk duration was significantly decreased compared with nondiabetic rats (0.77 ± 0.07 ng/mg wet weight aorta vs. 1.23 ± 0.11 ng/mg wet weight aorta, P < 0.001). Diabetic rats were treated with two doses of insulin, a lower dose of 8 U/kg/day that only partially corrected their plasma glucose and body weight compared with nondiabetic rats, and a higher dose of 25 U/kg/day that completely corrected their plasma glucose and body weight. Both insulin regimens completely reversed the defect in 6-oxo-PGF_1α production.

In the second series, the time course of development of the defect in 6-oxo-PGF_1α production was examined. It was found that two weeks after induction of diabetes, the aortic production of 6-oxo-PGF_1α did not differ between control and diabetic rats. However, 4 and 7 wk after induction of diabetes, 6-oxo-PGF_1α production was significantly reduced, even though the degree of hyperglycemia and hypoinsulinemia was the same as at 2 wk.

In the third series, the effect on aortic 6-oxo-PGF_1α production of weight loss caused by restricted dietary intake was compared with the effect of a comparable weight loss caused by experimental diabetes. Again, the diabetic rats had significantly reduced 6-oxo-PGF_1α production compared with control rats, but 6-oxo-PGF_1α production in nondiabetic rats which had lost weight as a result of limited feeding was the same as nondiabetic control rats fed ad libitum.

It is concluded (1) that insulin treatment, even if insufficient to achieve perfect control of plasma glucose, can restore 6-oxo-PGF_1α production to normal, (2) diabetes of greater than 2-wk duration is required to produce the abnormality, and (3) the reduced 6-oxo-PGF_1α production is not a nonspecific consequence of weight loss.