Impact of insulin or tolbutamide treatment on 14C-arachidonic acid conversion to prostacyclin and/or thromboxane in lungs, aortas, and platelets of streptozotocin-induced diabetic rats.
Diabetes is associated with a dramatic increase in the risk of thrombotic and atherosclerotic disease. The underlying factors responsible for this predisposition as well as the mechanisms involved have yet to be elucidated. Two endogenous substances, prostacyclin (PGI2) and thromboxane (TXA2), have recently been shown to possess significant vascular and thrombotic activity and are known to be altered in atherosclerosis, thrombotic conditions, and diabetes. We determined the conversion of 14C-arachidonic acid (AA) to PGI2 and TXA2 by lungs, aortas, and platelets obtained from chemically induced diabetic rats. In addition, we investigated the ability of insulin or tolbutamide to reverse these changes. Streptozotocin (STZ)-injected rats developed blood glucose levels 2-4 times that seen in normoglycemic controls. Intact perfused lungs isolated from rats beginning 7 days after STZ treatment synthesized 22-30% less PGI2 from 14C-AA. The ratio of PGI2/TXA2 was decreased in the diabetic rat lungs and was inversely proportional to plasma glucose levels at the time of death. Platelet TXA2 generation was increased 67% above control in diabetic rats while aortic PGI2 generation was decreased 28% below normoglycemic controls. Ten-day treatment with NPH insulin 20 U/kg s.c. in STZ-pretreated rats lowered plasma glucose toward normoglycemia more effectively than tolbutamide 200 mg/kg orally. Partial correction of the decreased pulmonary PGI2/TXA2 ratio seen in diabetic rats was produced by insulin and tolbutamide in proportion to their ability to lower blood glucose. At the doses employed, insulin caused aortic PI2 and platelet TXA2 generation from 14C-AA to approach that seen in mormoglycemic controls more effectively than tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D051381:Rats; D013928:Thromboxane A2 / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*; D014044:Tolbutamide / Q000494:pharmacology
D001095:Arachidonic Acids; D007328:Insulin; D013931:Thromboxanes; D013928:Thromboxane A2; D014044:Tolbutamide; D011464:Epoprostenol