Gene interactions and pathways from curated databases and text-mining
Am J Physiol Endocrinol Metab 2008, PMID: 18270303

Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice.

Koketsu, Yuko; Sakoda, Hideyuki; Fujishiro, Midori; Kushiyama, Akifumi; Fukushima, Yasushi; Ono, Hiraku; Anai, Motonobu; Kikuchi, Takako; Fukuda, Takeshi; Kamata, Hideaki; Horike, Nanao; Uchijima, Yasunobu; Kurihara, Hiroki; Asano, Tomoichiro

Several serine/threonine kinases reportedly phosphorylate serine residues of IRS-1 and thereby induce insulin resistance. In this study, to investigate the effect of mTOR/raptor on insulin signaling and metabolism in K/KAy mice with genetic obesity-associated insulin resistance, a dominant negative raptor, COOH-terminally deleted raptor (raptor-DeltaC(T)), was overexpressed in the liver via injection of its adenovirus into the circulation. Hepatic raptor-DeltaC(T) expression levels were 1.5- to 4-fold that of endogenously expressed raptor. Glucose tolerance in raptor-DeltaC(T)-overexpressing mice improved significantly compared with that of LacZ-overexpressing mice. Insulin-induced activation of p70S6 kinase (p70(S6k)) was significantly suppressed in the livers of raptor-DeltaC(T) overexpressing mice. In addition, insulin-induced IRS-1, Ser(307), and Ser(636/639) phosphorylations were significantly suppressed in the raptor-DeltaC(T)-overexpressing liver, whereas tyrosine phosphorylation of IRS-1 was increased. PI 3-kinase activation in response to insulin stimulation was increased approximately twofold, and Akt phosphorylation was clearly enhanced under both basal and insulin-stimulated conditions in the livers of raptor-DeltaC(T) mice. Thus, our data indicate that suppression of the mTOR/p70(S6k) pathway leads to improved glucose tolerance in K/KAy mice. These observations may contribute to the development of novel antidiabetic agents.

Diseases/Pathways annotated by Medline MESH: Glucose Intolerance, Insulin Resistance, Obesity
Document information provided by NCBI PubMed

Text Mining Data

Akt ⊣ raptor: " Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice "

insulin — mTOR/raptor: " In this study, to investigate the effect of mTOR/raptor on insulin signaling and metabolism in K/KAy mice with genetic obesity associated insulin resistance, a dominant negative raptor, COOH-terminally deleted raptor ( raptor-DeltaC ( T ) ), was overexpressed in the liver via injection of its adenovirus into the circulation "

insulin — mTOR/raptor: " In this study, to investigate the effect of mTOR/raptor on insulin signaling and metabolism in K/KAy mice with genetic obesity associated insulin resistance, a dominant negative raptor, COOH-terminally deleted raptor ( raptor-DeltaC ( T ) ), was overexpressed in the liver via injection of its adenovirus into the circulation "

p70 → Insulin: " Insulin induced activation of p70S6 kinase ( p70 ( S6k ) ) was significantly suppressed in the livers of raptor-DeltaC ( T ) overexpressing mice "

IRS-1 → insulin: " In addition, insulin induced IRS-1 , Ser ( 307 ), and Ser ( 636/639 ) phosphorylations were significantly suppressed in the raptor-DeltaC ( T ) -overexpressing liver, whereas tyrosine phosphorylation of IRS-1 was increased "

PI 3-kinase → insulin: " PI 3-kinase activation in response to insulin stimulation was increased approximately twofold, and Akt phosphorylation was clearly enhanced under both basal and insulin stimulated conditions in the livers of raptor-DeltaC ( T ) mice "

Manually curated Databases

No curated data.