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Visit our Expo - Redox and Inflammation signaling 2012

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Session III : Protein kinase cascades as therapeutic targets Poster III, 67<br />

Renal Akt kinase <strong>signaling</strong> in Zucker diabetic fatty rats (ZDF).<br />

Jana Zdychova1, Jessie N. Lindsley2, Sharon Anderson2, Radko Komers1,2.<br />

1Diabetes Center, Institute for Clinical <strong>and</strong> Experimental Medicine, 140 21 Prague 4,<br />

Czech Republic; 2Division of Nephrology <strong>and</strong> Hypertension, Oregon Health&Science<br />

University, 97239 Portl<strong>and</strong>, OR, USA. E-mail: rako@medicon.cz<br />

Impaired insulin <strong>signaling</strong> via PI-3-kinase (PI3K) <strong>and</strong> Akt in skeletal muscle, liver <strong>and</strong> fat has<br />

been implicated in the pathophysiology of insulin resistance (IR) including Type 2 diabetes<br />

(DM2). Kidney is also a target of insulin actions. However, unlike the skeletal muscle, renal<br />

Akt <strong>signaling</strong> in DM2 has been so far less studied. To address this issue, renal cortical activity<br />

<strong>and</strong> protein expression of Akt, its down-stream effector mTOR, <strong>and</strong> Akt antagonist PTEN<br />

were studied in 4 <strong>and</strong> 12-week old ZDF (ZDF4 <strong>and</strong> ZDF12), a model of DM2, <strong>and</strong> in agematched<br />

controls (Zucker lean, ZL4 <strong>and</strong> ZL12). Akt <strong>and</strong> mTOR activities were also studied in<br />

separate groups of 12 week old animals after a short-term treatment with PI3K inhibitor<br />

wortmannin (W, 100 µg/kg bwt) or vehicle (DMSO). Akt activity (in vitro kinase assay) <strong>and</strong><br />

expression of active Akt (P-Akt) were increased in ZDF12 as compared to ZL12 (p

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