Effect of obesity on insulin signaling through JAK2 in rat aorta.
Pathway specific resistance to insulin signaling through PI 3-kinase/Akt/eNOS associated with a normal or hyper-activated MAP kinase signaling in vascular tissues has recently been proposed as a candidate link between cardiovascular disease and insulin resistance. Growth stimulatory pathways other than ERK/MAP kinase, such as JAK/STAT have not yet been investigated in vessels of animal models of insulin resistance. Here we have examined whether insulin is able to activate JAK2/STAT pathway in rat aorta and also the regulation of this pathway in an animal model of obesity/insulin resistance. Our results demonstrate that insulin activates JAK2 tyrosine kinase activity in rat aorta in parallel with the activation of STAT3 and STAT5a/b. Moreover, it is shown that, in obese animals, JAK2/STAT and MAP kinase pathways are hyper-activated in response to insulin, which occurs in association with a reduced activation of PI 3-kinase/Akt pathway in aorta. The results of the present study suggest that, besides ERK/MAP kinase pathway, another potentially pro-atherogenic pathway, JAK2/STAT is hyper-activated in vessels in a state of insulin resistance and this phenomenon, in association with the inhibition of the PI 3-kinase/Akt pathway, may play an important role in the pathogenesis of cardiovascular diseases.
Gottardello Zecchin
Henrique
H
Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Cidade Universitária, Campinas, São Paulo, 13083-970, Brazil.
De Souza
Claudio Teodoro
CT
Oliveira Prada
Patrícia
P
Campello Carvalheira
José Barreto
JB
Augusto Velloso
Licio
L
Abdalla Saad
Mario José
MJ
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D004032:Diet; D005951:Glucose Tolerance Test; D047468:Immunoprecipitation; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D053614:Janus Kinase 2; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases