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Abstract:

Mammalian insulin-degrading enzyme (IDE) cleaves insulin, among other peptidic substrates, but its function in insulin signaling is elusive. We use the Drosophila system to define the function of IDE in the regulation of growth and metabolism. We find that either loss or gain of function of Drosophila IDE (dIDE) can restrict growth in a cell-autonomous manner by affecting both cell size and cell number. dIDE can modulate Drosophila insulin-like peptide 2 levels, thereby restricting activation of the phosphatidylinositol-3-phosphate ki nase pathway and promoting activation of Drosophila forkhead box, subgroup O transcription factor. Larvae reared in high sucrose exhibit delayed developmental timing due to insulin resistance. We find that dIDE loss of function exacerbates this phenotype and that mutants display increased levels of circulating sugar, along with augmented expression of a lipid biosynthesis marker. We propose that dIDE is a modulator of insulin signaling and that its loss of function favors insulin resistance, a hallmark of diabetes mellitus type II. © 2014 Galagovsky et al.

Registro:

Documento: Artículo
Título:The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner
Autor:Galagovsky, D.; Katz, M.J.; Acevedo, J.M.; Sorianello, E.; Glavic, A.; Wappner, P.
Filiación:Instituto Leloir, Buenos Aires C1405BWE, Argentina
National Scientific and Technical Research Council, Buenos Aires C1033AAJ, Argentina
Centro FONDAP de Regulación del Genoma, Facultad de Ciencias, Universidad de Chile, Santiago 7800024, Chile
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires C1053ABJ, Argentina
Palabras clave:insulin; insulin like peptide 2; insulinase; phosphatidylinositol 3 kinase; sucrose; sugar; transcription factor FOXO; unclassified drug; article; cell count; cell membrane; cell size; controlled study; cytoplasm; down regulation; Drosophila; enzyme activation; insulin resistance; larva; nonhuman; phenotype; priority journal; protein expression; Animals; Cell Size; Drosophila melanogaster; Drosophila Proteins; Gene Expression Regulation, Developmental; Insulysin; Larva; Phenotype; Phosphatidylinositol 3-Kinases; Signal Transduction; Wing
Año:2014
Volumen:25
Número:6
Página de inicio:916
Página de fin:924
DOI: http://dx.doi.org/10.1091/mbc.E13-04-0213
Título revista:Molecular Biology of the Cell
Título revista abreviado:Mol. Biol. Cell
ISSN:10591524
CODEN:MBCEE
CAS:insulin, 9004-10-8; insulinase, 9013-83-6; phosphatidylinositol 3 kinase, 115926-52-8; sucrose, 122880-25-5, 57-50-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10591524_v25_n6_p916_Galagovsky

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Citas:

---------- APA ----------
Galagovsky, D., Katz, M.J., Acevedo, J.M., Sorianello, E., Glavic, A. & Wappner, P. (2014) . The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner. Molecular Biology of the Cell, 25(6), 916-924.
http://dx.doi.org/10.1091/mbc.E13-04-0213
---------- CHICAGO ----------
Galagovsky, D., Katz, M.J., Acevedo, J.M., Sorianello, E., Glavic, A., Wappner, P. "The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner" . Molecular Biology of the Cell 25, no. 6 (2014) : 916-924.
http://dx.doi.org/10.1091/mbc.E13-04-0213
---------- MLA ----------
Galagovsky, D., Katz, M.J., Acevedo, J.M., Sorianello, E., Glavic, A., Wappner, P. "The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner" . Molecular Biology of the Cell, vol. 25, no. 6, 2014, pp. 916-924.
http://dx.doi.org/10.1091/mbc.E13-04-0213
---------- VANCOUVER ----------
Galagovsky, D., Katz, M.J., Acevedo, J.M., Sorianello, E., Glavic, A., Wappner, P. The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner. Mol. Biol. Cell. 2014;25(6):916-924.
http://dx.doi.org/10.1091/mbc.E13-04-0213