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Abstract
Glomeruli isolated from streptozotocin-diabetic rats produced significantly greater
amounts of immunoreactive prostaglandin (PG)E2, PGF2α, and prostacyclin (PGI2) measured as the stable metabolite 6-keto-PGF1α 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 PGE2 (57–72%) with PGE2 > PGF2α > PGI2 after stimulation of acylhydrolase with melittin. Mesangial cells from diabetic rats
produced predominantly PGI2 (55–73%) with PGI2 > PGE2 > PGF2α. 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
, normal mesangial cell's produced proportionately greater amounts of PGE2, PGF2α and PGI2; no alteration to predominantly PGI2 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. PGE2 production increased to a greater degree than PGI2. With insulin present in the high-glucose condition, there was a disproportional
attenuation of all prostaglandins produced, with PGI2 decreasing more than PGE2. Thus, the streptozotocin-induced diabetic state resulted in an alteration in mesangial
cell arachidonic acid metabolism.

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© 1983 Published by Elsevier Inc.