Increased release of prostaglandins from the mesenteric vascular bed of diabetic animals: the effects of glucose and insulin.
To study prostaglandin (PG) metabolism in peripheral vascular beds, PGs and TxB2 released from perfused mesenteric tissues were measured in both normal and streptozotocin (STZ)-induced diabetic rats. The release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) was significantly increased in mesenteric vascular beds from diabetics in comparison with control rats. The 6-keto-PGF1 alpha/TxB2 ratio was decreased in diabetics. In order to clarify the mechanism of this imbalanced synthesis of eicosanoids, we infused buffer with 500 mg/dl glucose which was similar to the concentration of blood glucose in the diabetic rats. In response to this high glucose concentration, TxB2 released into the effluent from the mesenteric beds of normal animals was increased to the diabetic level. The release of the other PGs was not changed significantly. The 6-keto-PGF1 alpha/TxB2 ratio was decreased in control rats perfused with buffer containing 500 mg/dl glucose. We also investigated the effect of insulin (50 and 100 microU/ml) in the diabetic mesenteric vascular beds, but there were no changes in prostaglandin or TxB2 release. These data suggest that a high glucose level may have an important role in regulating TxA2 synthesis and in modulating the balance between PGI2 and TxA2 in diabetes. It is postulated that an increase in the micro-circulation of PGI2 may partially be protective against the progression of angiopathy.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015232:Dinoprostone; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation; D013929:Thromboxane B2 / Q000378:metabolism
D007328:Insulin; D011453:Prostaglandins; D011458:Prostaglandins E; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D005947:Glucose; D015232:Dinoprostone