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01.04.2003 | Article

Insulin signalling pathways in aorta and muscle from two animal models of insulin resistance—the obese middle-aged and the spontaneously hypertensive rats

verfasst von: H. G. Zecchin, R. M. N. Bezerra, J. B. C. Carvalheira, M. A. Carvalho-Filho, K. Metze, K. G. Franchini, M. J. A. Saad

Erschienen in: Diabetologia | Ausgabe 4/2003

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Abstract

Aims/hypothesis

The aim of this study was to investigate insulin signalling pathways directly in vivo in skeletal muscle and thoracic aorta from obese middle-aged (12-month-old) rats, which have insulin resistance but not cardiovascular disease, and from spontaneously hypertensive rats (SHR), an experimental model of insulin resistance and cardiovascular disease.

Methods

We have used in vivo insulin infusion, followed by tissue extraction, immunoprecipitation and immunoblotting.

Results

Obese middle-aged rats and the SHR showed marked insulin resistance, which parallels the reduced effects of this hormone in the insulin signalling cascade in muscle. In aortae from obese middle-aged rats, the PI 3-kinase/Akt pathway is preserved, leading to a normal activation of endothelial nitric oxide synthase. In SHR this pathway is severely blunted, with reductions in eNOS protein concentration and activation. Both animals, however, showed higher concentrations and higher tyrosine phosphorylation of mitogen-activated protein (MAP) kinase isoforms in aortae.

Conclusions/interpretation

Alterations in the IRS/PI 3-K/Akt pathway in muscle of 12-month-old rats and SHR could be involved in the insulin resistance of these animals. The preservation of this pathway in aorta of 12-month-old rats, apart from increases in MAP kinase protein concentration and activation, could be a factor that contributes to explaining the absence of cardiovascular disease in this animal model. However, in aortae of SHR, the reduced insulin signalling through IRS/PI 3-kinase/Akt/eNOS pathway could contribute to the endothelial dysfunction of this animal.

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Titel: Insulin signalling pathways in aorta and muscle from two animal models of insulin resistance—the obese middle-aged and the spontaneously hypertensive rats
verfasst von: H. G. Zecchin
R. M. N. Bezerra
J. B. C. Carvalheira
M. A. Carvalho-Filho
K. Metze
K. G. Franchini
M. J. A. Saad
Publikationsdatum: 01.04.2003
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 4/2003
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-003-1073-0

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Insulin signalling pathways in aorta and muscle from two animal models of insulin resistance—the obese middle-aged and the spontaneously hypertensive rats