التفاصيل البيبلوغرافية
| العنوان: |
Hindbrain GLP-1 receptor-mediated suppression of food intake requires a PI3K-dependent decrease in phosphorylation of membrane-bound Akt. |
| المؤلفون: |
Rupprecht, Laura E., Mietlicki-Baase, Elizabeth G., Zimmer, Derek J., McGrath, Lauren E., Olivos, Diana R., Hayes, Matthew R. |
| المصدر: |
American Journal of Physiology: Endocrinology & Metabolism; Sep2013, Vol. 305 Issue 6, pE751-E759, 9p |
| مصطلحات موضوعية: |
RHOMBENCEPHALON, GLUCAGON-like peptide-1 receptor, INGESTION, PHOSPHORYLATION, MEMBRANE proteins, PROTEIN kinase B |
| مستخلص: |
Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) expressed in the nucleus tractus solitarius (NTS) are physiologically required for the control of feeding. Recently, NTS GLP-1R-mediated suppression of feeding was shown to occur via a rapid PKA-induced suppression of AMPK and activation of MAPK signaling. Unknown are the additional intracellular signaling pathways that account for the long-term hypophagic effects of GLP-1R activation. Because cAMP/PKA activity can promote PI3K/PIP3-dependent translocation of Akt to the plasma membrane, we hypothesize that hindbrain GLP-1R-mediated control of feeding involves a PI3K-Akt-dependent pathway. Importantly, the novel evidence presented here challenges the dogmatic view that PI3K phosphorylation results in an obligatory activation of Akt and instead supports a growing body of literature showing that activation of cAMP/PKA can inhibit Akt phosphorylation at the plasma membrane. Behavioral data show that inhibition of hindbrain PI3K activity by a fourth icv administration of LY-294002 (3.07 μg) attenuated the food intake- and body weight-suppressive effects of a fourth icv administration of the GLP-1R agonist exendin-4 (0.3 μg) in rats. Hindbrain administration of triciribine (10g), an inhibitor of PIP3-dependent translocation of Akt to the cell membrane, also attenuated the intakesuppressive effects of a fourth icv injection of exendin-4. Immunoblot analyses of ex vivo NTS tissue lysates and in vitro GLP-1Rexpressing neurons (GT1-7) support the behavioral findings and show that GLP-1R activation decreases phosphorylation of Akt in a timedependent fashion. Current data reveal the requirement of PI3K activation, PIP3-dependent translocation of Akt to the plasma membrane, and suppression in phosphorylation of membrane-bound Akt to mediate the food intake-suppressive effects of hindbrain GLP-1R activation. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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