Angiotensin II modulates tyr-phosphorylation of IRS-4, an insulin receptor substrate, in rat liver membranes

2006 ◽  
Vol 293 (1-2) ◽  
pp. 35-46 ◽  
Author(s):  
Rodrigo S. Villarreal ◽  
Sergio E. Alvarez ◽  
Maximiliano Juri Ayub ◽  
Gladys M. Ciuffo
Keyword(s):  
Angiotensin Ii ◽  
Insulin Receptor ◽  
Rat Liver ◽  
Insulin Receptor Substrate ◽  
Liver Membranes

scholarly journals Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3-kinase in rat heart

1995 ◽  
Vol 310 (3) ◽  
pp. 741-744 ◽  
Author(s):  
M J A Saad ◽  
L A Velloso ◽  
C R O Carvalho
Keyword(s):  
Angiotensin Ii ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Rat Heart ◽  
Fold Increase ◽  
At1 Receptor ◽  
Insulin Receptor Substrate ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Receptor Substrate 1

We have investigated whether angiotensin II (AII) is able to induce insulin receptor substrate 1 (IRS-1) phosphorylation and its association with phosphatidylinositol 3-kinase (PI 3-kinase) in the rat heart in vivo. The phosphorylation state of IRS-1 following infusion of insulin or AII via the vena cava was assessed after immunoprecipitation with an anti-peptide antibody to IRS-1 followed by immunoblotting with an anti-phosphotyrosine antibody and an anti-PI 3-kinase antibody. Densitometry indicated a 5.6 +/- 1.3-fold increase in IRS-1 phosphorylation after stimulation with AII and a 12.8 +/- 3.1-fold increase after insulin. The effect was maximal at an AII concentration of 10(-8) M and occurred 1 min after infusion. There was also a 6.1 +/- 1.2-fold increase in IRS-1-associated PI 3-kinase in response to AII. In the isolated perfused heart the result was similar, showing a direct effect of AII on this pathway. When the animals were pretreated for 1 h with DuP 753, a non-peptide AII-receptor 1 (AT1 receptor) antagonist, there was a marked reduction in the AII-induced tyrosine phosphorylation of IRS-1, suggesting that phosphorylation is initially mediated by the AT1 receptor. We conclude that AII stimulates tyrosine phosphorylation of IRS-1 and its association with PI 3-kinase. This pathway thus represents an additional signalling mechanism stimulated by AII in the rat heart in vivo.

Activation of PI 3-kinase in 3T3-L1 adipocytes by association with insulin receptor substrate-1

1994 ◽  
Vol 266 (3) ◽  
pp. E486-E494 ◽  
Author(s):  
L. Lamphere ◽  
C. L. Carpenter ◽  
Z. F. Sheng ◽  
R. G. Kallen ◽  
G. E. Lienhard
Keyword(s):  
Recombinant Protein ◽  
Insulin Receptor ◽  
Rat Liver ◽  
Insulin Treatment ◽  
Kinase Activity ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Enhanced Activity

Insulin treatment of adipocytes causes the rapid phosphorylation of the insulin receptor substrate-1 (IRS-1) on tyrosine. The phosphotyrosine [Tyr(P)] form of IRS-1 then complexes with the enzyme phosphatidylinositol (PI) 3-kinase. In this study, we have investigated the effect of this association on PI 3-kinase activity in 3T3-L1 adipocytes. Insulin stimulated cytosolic PI 3-kinase activity about sevenfold. This stimulation was maximal after 1 min of exposure of cells to insulin, persisted for at least 1 h, and occurred over the range of insulin concentrations that saturate its receptor. By means of immunoprecipitation of IRS-1, it was shown that virtually all of the enhanced activity was due to PI 3-kinase complexed with IRS-1. Moreover, the purified Tyr(P) form of IRS-1, either isolated from 3T3-L1 adipocytes or obtained by phosphorylation of the recombinant protein with the insulin receptor, markedly stimulated the activity of purified rat liver PI 3-kinase. These results show that the association of Tyr(P) IRS-1 with PI 3-kinase activates the enzyme and thereby can explain the elevation of PI 3,4-bisphosphate and PI 3,4,5-trisphosphate in vivo observed upon treatment of adipocytes with insulin.

Changes in tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 (IRS-1) and association of p85 subunit of phosphatidylinositol 3-kinase with IRS-1 after feeding in rat liver in vivo

1997 ◽  
Vol 154 (2) ◽  
pp. 267-273 ◽  
Author(s):  
Y Ito ◽  
M Ariga ◽  
S-I Takahashi ◽  
A Takenaka ◽  
T Hidaka ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Rat Liver ◽  
Insulin Receptor Substrate ◽  
Β Subunit ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Receptor Substrate 1 ◽  
Insulin Receptor Tyrosine Kinase ◽  
Phosphatidylinositol 3

Abstract The binding of insulin to its receptor rapidly induces intrinsic insulin receptor tyrosine kinase activity, resulting in tyrosine phosphorylation of various cytosolic substrates, such as insulin receptor substrate-1 (IRS-1) which, in turn, associates with a p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) followed by activation of this enzyme. In the present study, we have examined these early steps of insulin signalling in rat liver in vivo after food ingestion. After fasting for 22 h, a 12% casein diet was available ad libitum throughout the 8-h experimental period. Plasma insulin concentrations increased within 45 min after feeding, reached a maximum at 1·5 h and gradually decreased until 8 h. Autophosphorylation of the insulin receptor β-subunit in liver was detected even during fasting and increased about 1·5-fold at 1·5 h after feeding. Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Because tyrosine phosphorylation of the insulin receptor β-subunit and IRS-1 and the association of the p85 subunit of PI 3-kinase with IRS-1 in liver were closely correlated with the changes in the plasma concentration of insulin, we concluded that endogenous insulin secreted in response to eating caused these insulin-dependent intracellular changes in the liver. Journal of Endocrinology (1997) 154, 267–273

Sign in / Sign up

Export Citation Format

Share Document