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- Title
Altered expression levels and impaired steps in the pathway to phosphatidylinositol 3-kinase activation via insulin receptor substrates 1 and 2 in Zucker fatty rats.
- Authors
Anai, Motonobu; Funaki, Makoto; Ogihara, Takehide; Terasaki, Jungo; Inukai, Kouichi; Katagiri, Hideki; Fukushima, Yasushi; Yazaki, Yoshio; Kikuchi, Masatoshi; Oka, Yoshitomo; Asano, Tomoichiro; Anai, M; Funaki, M; Ogihara, T; Terasaki, J; Inukai, K; Katagiri, H; Fukushima, Y; Yazaki, Y; Kikuchi, M
- Abstract
To elucidate the mechanism of obesity-related insulin resistance, we investigated the impaired steps in the processes of phosphatidylinositol (PI) 3-kinase activation through binding with insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in liver and muscle of Zucker fatty rats. The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. Despite the decrease in the tyrosine phosphorylation levels of hepatic IRS-1 and IRS-2 being mild to moderate, associated PI 3-kinase activities were dramatically decreased in fatty rats (IRS-1, 14%; IRS-2, 10%), which may suggest alteration in the sites of phosphorylated tyrosine residues of hepatic IRS-1 and IRS-2. In addition, we demonstrated that the expressions of p85alpha and p55alpha regulatory subunits of PI 3-kinase were reduced (p85alpha, 67%; p55alpha, 54%), and that the p50alpha regulatory subunit was markedly upregulated (176%) in the livers of fatty rats without apparent alterations in expressions of the catalytic subunits p110alpha and p110beta. These alterations may reflect the obesity-related insulin resistance commonly observed in human NIDDM.
- Subjects
PHOSPHOINOSITIDES; INSULIN receptors
- Publication
Diabetes, 1998, Vol 47, Issue 1, p13
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diab.47.1.13