Effect of prolonged uremia on insulin-like growth factor-I receptor autophosphorylation and tyrosine kinase activity in kidney and muscle.
Recently, based on a study in rats with chronic renal failure (CRF), it has been suggested that IGF-I resistance in uremia may be caused in part by defective IGF-I receptor autophosphorylation and tyrosine kinase activity. Thus if such a defect were to develop in prolonged acute renal failure (ARF), this may explain why IGF-I therapy, effective in rats, has failed to promote recovery from ARF in patients. Accordingly, we examined IGF-I receptor function in rats with uremia of increasing duration and in pair-fed sham-operated controls. After 6 days of prolonged ARF, kidney IGF-I receptor binding increased twofold, while IGF-I stimulated receptor phosphorylation and tyrosine kinase activity were unchanged. Muscle receptor binding, autophosphorylation and tyrosin kinase activity were similar to control values after 6 or even 21 days of uremia. Taking all these findings together it appears that IGF-I resistance in uremia cannot be attributed to a receptor defect. This in turn argues against altered receptor function as a cause of the failure of IGF-I to modify clinical ARF.
Tsao
Tanny
T
Research Service Veterans Affairs Palo Alto Health Care System, Calif 94304, USA.
Fervenza
Fernando
F
Friedlaender
Michael
M
Chen
Yu
Y
Rabkin
Ralph
R
D058186:Acute Kidney Injury / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012995:Solubility; D014511:Uremia / Q000378:metabolism*
D007334:Insulin-Like Growth Factor I; D003404:Creatinine; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1