PMID- 12897373
OWN - NLM
STAT- MEDLINE
DCOM- 20040413
LR  - 20211203
IS  - 1355-008X (Print)
IS  - 1355-008X (Linking)
VI  - 21
IP  - 2
DP  - 2003 Jul
TI  - Regulation of insulin receptor substrate-2 tyrosine phosphorylation in animal 
      models of insulin resistance.
PG  - 115-22
AB  - Insulin induces a wide variety of growth and metabolic responses in many cell 
      types. These actions are initiated by insulin binding to its receptor and involve 
      a series of alternative and complementary pathways created by the multiple 
      substrates of the insulin receptor (insulin receptor substrates [IRSs]). We 
      investigated IRS-1 and IRS-2 tyrosine phosphorylation; their association with 
      phosphatidylinositol-3-OH kinase (PI3-K); and the phosphorylation of Akt, a 
      serine-threonine kinase situated downstream of PI3-K, in liver and muscle of two 
      animal models of insulin resistance: epinephrine- or dexamethasone-treated rats. 
      We used in vivo insulin infusion followed by tissue extraction, 
      immunoprecipitation, and immunoblotting. IRS-1 and IRS-2 protein expression did 
      not change in liver and muscle of the epinephrine- treated rats, but in 
      dexamethasone-treated rats IRS-1 presented an increase in liver and a decrease in 
      muscle tissue. PI3-K and Akt protein expression did not change in liver or muscle 
      of the two animal models of insulin resistance. There was a downregulation in 
      insulin- induced IRS-1 and IRS-2 tyrosine phosphorylation and association with 
      PI3-K in both models of insulin resistance. In parallel, insulin-induced Akt 
      phosphorylation was reduced in both tissues of epinephrine-treated rats, and in 
      liver but not in muscle of dexamethasonetreated rats. The reduction in 
      insulin-induced Akt phosphorylation may help to explain the insulin resistance in 
      liver and muscle of epinephrine-treated rats and in the liver of 
      dexamethasone-treated rats.
FAU - Rojas, Fernanda Alvarez
AU  - Rojas FA
AD  - Departamento de Clinica Medica, FCM, UNICAMP, Campinas, SP, Brasil.
FAU - Hirata, Aparecida Emiko
AU  - Hirata AE
FAU - Saad, Mario J A
AU  - Saad MJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrine
JT  - Endocrine
JID - 9434444
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (Irs2 protein, rat)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Animals
MH  - Dexamethasone/pharmacology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Epinephrine/physiology
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin Resistance/*physiology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Liver/drug effects/enzymology/metabolism
MH  - Male
MH  - Muscle, Skeletal/drug effects/enzymology/metabolism
MH  - Phosphatidylinositol 3-Kinases/drug effects/*metabolism
MH  - Phosphoproteins/drug effects/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Serine-Threonine Kinases/drug effects/metabolism
MH  - Proto-Oncogene Proteins/drug effects/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Rats, Wistar
MH  - Tyrosine/*metabolism
EDAT- 2003/08/05 05:00
MHDA- 2004/04/14 05:00
CRDT- 2003/08/05 05:00
PHST- 2002/08/29 00:00 [received]
PHST- 2003/12/18 00:00 [revised]
PHST- 2003/01/15 00:00 [accepted]
PHST- 2003/08/05 05:00 [pubmed]
PHST- 2004/04/14 05:00 [medline]
PHST- 2003/08/05 05:00 [entrez]
AID - ENDO:21:2:115 [pii]
AID - 10.1385/ENDO:21:2:115 [doi]
PST - ppublish
SO  - Endocrine. 2003 Jul;21(2):115-22. doi: 10.1385/ENDO:21:2:115.