Research Article| Volume 11, ISSUE 4, P431-442, August 1983

The effects of insulin, glucose and diabetes on prostaglandin production by rat kidney glomeruli and cultured glomerular mesangial cells

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      Glomeruli isolated from streptozotocin-diabetic rats produced significantly greater amounts of immunoreactive prostaglandin (PG)E2, PGF, and prostacyclin (PGI2) measured as the stable metabolite 6-keto-PGF 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 > PGF > PGI2 after stimulation of acylhydrolase with melittin. Mesangial cells from diabetic rats produced predominantly PGI2 (55–73%) with PGI2 > PGE2 > PGF. 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 Math Eq, normal mesangial cell's produced proportionately greater amounts of PGE2, PGF 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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