The insulin-like growth factor-I axis in acute renal failure.
We have examined the response of the renal insulin-like growth factor (IGF-I) axis to acute ischemic injury in the rat Key findings included a decrease in IGF-I mRNA and peptide levels, a decrease in GH receptor gene plus protein expression and a decrease in the IGF binding proteins except for IGF binding protein I. Administration of GH to compensate for the reduced GH receptor binding corrected the IGF-I mRNA levels suggesting a relative GH deficiency. Interestingly, IGF-I receptor mRNA levels were unchanged while plasma membrane IGF-I receptor number increased two fold. This appeared to be due to a redistribution of receptors to a membrane location. IGF-I receptor autophosphorylation and tyrosine kinase activity were intact despite severe uremia for up to 6 days. We propose that this increase of functional IGF-I receptors following acute tubular necrosis will sensitize the kidney to the administration of exogenous IGF-I.
Friedlaender
M M
MM
Research Service Veterans Affairs, Palo Alto Health Care System, California, USA.
Fervenza
F C
FC
Tsao
T
T
Hsu
F
F
Rabkin
R
R
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D004815:Epidermal Growth Factor / Q000627:therapeutic use; D013006:Growth Hormone / Q000008:administration & dosage; D007150:Immunohistochemistry; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1