Insulin and other regulatory factors modulate the growth and the phosphoenolpyruvate carboxykinase (PEPCK) activity of primary rabbit kidney proximal tubule cells in serum free medium.
Insulin was observed to modulate the growth and the phosphoenolpyruvate carboxykinase (PEPCK) activity of primary cultures of rabbit renal proximal tubule cells in serum free medium. Insulin was stimulatory to primary proximal tubule cell growth at a concentration of 10(-8) M. In contrast, insulin was inhibitory to a proximal tubule function, PEPCK activity, following a 5-minute incubation period. An insulin dosage as low as 10(-10) M was inhibitory to PEPCK activity, suggesting the involvement of insulin receptors. Although insulin was required at a significantly higher dosage to stimulate the growth of the primary renal proximal tubule cells than to inhibit PEPCK activity, the elevated dosage required in order to observe a growth effect may be explained by the degradation of insulin by the primary renal proximal tubule cells. However the possible involvement of receptors for Insulin-like Growth Factor I (IGF-I) and Insulin-like Growth Factor II (IGF-II) in mediating the effects of insulin cannot be excluded. Other effector molecules were also examined with respect to their effects on PEPCK activity. The possible involvement of cyclic AMP in the control of the PEPCK activity of the primary renal cells was indicated by the stimulatory effects of 8 bromocyclic AMP, isobutyl methylxanthine (a cyclic AMP phosphodiesterase inhibitor), and forskolin (an activator of adenylate cyclase). Phorbol 12-myristate 13-acetate (TPA), which activates protein kinase C, was inhibitory. The actions of these effector molecules and insulin on the PEPCK activity of the primary renal cultures are remarkably similar to their effects on hepatic PEPCK. Several growth factors, fibroblast growth factor (FGF), and transforming growth factor beta (TGF beta) were also examined. FGF was observed to be stimulatory, whereas TGF beta was inhibitory to the PEPCK activity of the primary renal proximal tubule cells.
Wang
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Y
Biochemistry Department, State University of New York, Buffalo 14214.
Taub
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M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001769:Blood; D002455:Cell Division / Q000502:physiology; D002458:Cell Fractionation; D002478:Cells, Cultured; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D011972:Receptor, Insulin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003470:Culture Media; D006133:Growth Substances; D007328:Insulin; D000242:Cyclic AMP; D011972:Receptor, Insulin; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine