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01.12.2003 | Article

Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats

verfasst von: J. B. C. Carvalheira, E. B. Ribeiro, E. P. Araújo, R. B. Guimarães, M. M. Telles, M. Torsoni, J. A. R. Gontijo, L. A. Velloso, M. J. A. Saad

Erschienen in: Diabetologia | Ausgabe 12/2003

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Abstract

Aim/hypothesis

By acting in the brain, insulin suppresses food intake. However, little is known with regard to insulin signalling in the hypothalamus in insulin-resistant states.

Methods

Western blotting, immunohistochemistry and polymerase chain reaction assays were combined to compare in vivo hypothalamic insulin signalling through the PI3-kinase and MAP kinase pathways between lean and obese Zucker rats.

Results

Intracerebroventricular insulin infusion reduced food intake in lean rats to a greater extent than that observed in obese rats, and pre-treatment with PI3-kinase inhibitors prevented insulin-induced anorexia. The relative abundance of IRS-2 was considerably higher than that of IRS-1 in hypothalamus of both lean and obese rats. Insulin-stimulated phosphorylation of IR, IRS-1/2, the associations of PI 3-kinase to IRS-1/2 and phosphorylation of Akt in hypothalamus were decreased in obese rats compared to lean rats. These effects seem to be mediated by increased phosphoserine content of IR, IRS-1/2 and decreased protein levels of IRS-1/2 in obese rats. In contrast, insulin stimulated the phosphorylation of MAP kinase equally in lean and obese rats.

Conclusion/interpretation

This study provides direct measurements of insulin signalling in hypothalamus, and documents selective resistance to insulin signalling in hypothalamus of Zucker rats. These findings provide support for the hypothesis that insulin could have anti-obesity actions mediated by the PI3-kinase pathway, and that impaired insulin signalling in hypothalamus could play a role in the development of obesity in this animal model of insulin-resistance.

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Titel: Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats
verfasst von: J. B. C. Carvalheira
E. B. Ribeiro
E. P. Araújo
R. B. Guimarães
M. M. Telles
M. Torsoni
J. A. R. Gontijo
L. A. Velloso
M. J. A. Saad
Publikationsdatum: 01.12.2003
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 12/2003
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-003-1246-x

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Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats

Abstract

Aim/hypothesis

Methods

Results

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Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

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Antihypertensiva schützen auch alte Menschen noch vor Demenz

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