Abstract
Glomeruli isolated from streptozotocin-diabetic rats produced significantly greater amounts of immunoreactive prostaglandin (PG)E 2, PGF 2α, and prostacyclin (PGI 2) measured as the stable metabolite 6-keto-PGF 1α than control glomeruli. These data led to studies to determine whether the vasoactive glomerular mesangial cell exhibited alterations in arachidonic acid metabolism in diabetes. Therefore, we isolated and cultured under identical conditions, mesangial cells from normal and streptozotocin-diabetic rats. Normal mesangial cells produced predominantly PGE 2 (57–72%) with PGE 2 > PGF 2α > PGI 2 after stimulation of acylhydrolase with melittin. Mesangial cells from diabetic rats produced predominantly PGI 2 (55–73%) with PGI 2 > PGE 2 > PGF 2α. A similar prostaglandin profile was obtained when arginine vasopressin (AVP) was used to stimulate acylhydrolase activity. In addition, diabetic mesangial cells synthesized greater amounts of prostaglandins than normal mesangial cells cultured for the same number of passages. When cultured under high-glucose conditions (in tissue culture medium with a final glucose concentration of 550 mg/dl) to mimic the diabetic state in vitro , normal mesangial cell's produced proportionately greater amounts of PGE 2, PGF 2α and PGI 2; no alteration to predominantly PGI 2 production was observed. Insulin addition to the high-glucose condition tended to attenuate prostaglandin production. Diabetic mesangial cells likewise produced more prostaglandins when cultured under high-glucose conditions; however, the increases were not proportional among the 3 prostaglandins examined. PGE 2 production increased to a greater degree than PGI 2. With insulin present in the high-glucose condition, there was a disproportional attenuation of all prostaglandins produced, with PGI 2 decreasing more than PGE 2. Thus, the streptozotocin-induced diabetic state resulted in an alteration in mesangial cell arachidonic acid metabolism.
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