Tissue-specific regulation of IRS-1 in unilaterally nephrectomized rats.
Insulin stimulates the tyrosine kinase activity of its receptor, resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate 1 (IRS-1). IRS-1 is also a substrate for different peptides and growth factors, and a transgenic mouse "knockout" for this protein does not have normal growth. However, the role of IRS-1 in kidney hypertrophy and/or hyperplasia was not investigated. In the present study we investigated IRS-1 protein and tyrosine phosphorylation levels in the remnant kidney after unilateral nephrectomy (UNX) in 6-week-old male Wistar rats. After insulin stimulation the levels of insulin receptor and IRS-1 tyrosine phosphorylation were reduced to 79 +/- 5% (P < 0.005) and 58 +/- 6% (P < 0.0001), respectively, of the control (C) levels, in the remnant kidney. It is possible that a circulating factor and/or a local (paracrine) factor playing a role in kidney growth can influence the early steps of insulin action in parallel. To investigate the hypothesis of a circulating factor, we studied the early steps of insulin action in liver and muscle of unilateral nephrectomized rats. There was no change in pp185 tyrosine phosphorylation levels in liver (C 100 +/- 12% vs UNX 89 +/- 9%, NS) and muscle (C 100 +/- 22% vs UNX 91 +/- 17%, NS), and also there was no change in IRS-1 phosphorylation levels in both tissues. These data demonstrate that after unilateral nephrectomy there is a decrease in insulin-induced insulin receptor and IRS-1 tyrosine phosphorylation levels in kidney but not in liver and muscle. It will be of interest to investigate which factors, probably paracrine ones, regulate these early steps of insulin action in the contralateral kidney of unilaterally nephrectomized rats.
Sasse
A D
AD
Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brasil.
Chen
E
E
Carvalho
C R
CR
Gontijo
J A
JA
Brenelli
S L
SL
Saad
M J
MJ
D000818:Animals; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000502:physiology*
D011972:Receptor, Insulin