Insulin stimulates phosphate transport in opossum kidney epithelial cells.
Insulin is antiphosphaturic in vivo and this effect is due, in part, to increased Na(+)-dependent phosphate uptake across the luminal brush-border membrane of the proximal tubule. The intracellular mechanism is not understood. The present study shows that the stimulatory effect of insulin on phosphate transport can be reproduced in opossum kidney (OK) cells, suggesting that this established renal epithelial cell line may be a good model for further studies on insulin action on renal phosphate transport. The stimulation by insulin was dose related when insulin was used at concentrations within the range of 10(-14) to 10(-8) M. At 10(-8) M, insulin had no effect on Na(+)-independent uptake of phosphate or on the Na(+)-dependent uptakes of methyl-alpha-D-glucopyranoside and glutamate. The onset of insulin action on phosphate uptake was detected within 15 min, and the stimulation was reversed completely within 30 min after removal of insulin from the medium. Insulin action was not blocked by protein synthesis inhibitors and was not altered by bacitracin, an inhibitor of intracellular degradation of insulin. Pretreatment with the calcium-channel blockers, nifedipine and verapamil (10(-4) M), produced significant increases in the stimulatory effect of insulin, suggesting indirectly that insulin action on phosphate uptake may be influenced by Ca2+. In contrast to in vivo studies, there was no evidence that insulin interfered with parathyroid hormone action on OK cells.
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46223.
M I
MI
Abraham
J A
JA
McAteer
S A
SA
Kempson
D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D001692:Biological Transport; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D009893:Opossums; D009994:Osmolar Concentration; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D014176:Protein Biosynthesis; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D007328:Insulin; D010281:Parathyroid Hormone; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D001414:Bacitracin