DIET AND DISEASE ALTER PHOSPHOINOSITIDE COMPOSITION AND METABOLISM INMURINE POLYCYSTIC KIDNEYS

Because diet can affect the progression of polycystic kidney disease ( PKD) and because renal phosphoinositide metabolism is altered in mice with PKD, the effects of diet and disease on phosphoinositide composit ion and metabolism were examined in kidneys of mice with PKD. The phos phatidylinositol-phosphate (PIP) to phosphatidylinositol (PI) molar ra tio was higher (0.034 +/- 0.003 vs. 0.023 +/- 0.001, P < 0.01) and the PI-bisphosphate (PIP2) to PIP molar ratio was lower (0.70 +/- 0.08 vs . 1.19 +/- 0.10, P < 0.05) in kidneys of mice with PKD [DBA/2FG-pcy (p cy)] compared with normal controls (DBA/2J). When initial incorporatio n (reflecting synthesis) of [H-3]inositol into renal phosphoinositides in mice injected with [H-3]inositol was measured, the [H-3]PIP to [H- 3]PI ratio was higher in the diseased kidneys compared with normal kid neys (0.016 +/- 0.001 vs. 0.013 +/- 0.001, P < 0.05), whereas the [H-3 ]PIP2 to [H-3]PIP ratio was not significantly different. In a study us ing dietary manipulations that alter the progression of PKD in pcy mic e (6 vs. 25% casein and sunflower seed oil vs. fish oil in a 2 x 2 des ign), animals were injected intraperitoneally with [H-3]inositol 5 h b efore killing. In these animals, the [H-3]PIP2 to [H-3]PIP ratio seeme d to be the best indicator of disease progression. In addition, kidney weight (as altered by diet) was positively correlated (r = 0.62, P = 0.02) with the level of the [H-3]PI-3-P isomer relative to total [H-3] PIP in the kidney. These results demonstrate that alterations in dieta ry protein level and lipid composition can modulate renal phosphoinosi tide signal transduction in mice with PKD.