The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner

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 Drosophi...

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Autores principales:	Galagovsky, Diego, Acevedo, Julieta María, Sorianello, Eleonora Mariana, Wappner, Pablo
Publicado:	2014
Materias:	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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10591524_v25_n6_p916_Galagovsky http://hdl.handle.net/20.500.12110/paper_10591524_v25_n6_p916_Galagovsky
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_10591524_v25_n6_p916_Galagovsky
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spelling	paper:paper_10591524_v25_n6_p916_Galagovsky2023-06-08T16:03:24Z The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner Galagovsky, Diego Acevedo, Julieta María Sorianello, Eleonora Mariana Wappner, Pablo 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 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. Fil:Galagovsky, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Acevedo, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Sorianello, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10591524_v25_n6_p916_Galagovsky http://hdl.handle.net/20.500.12110/paper_10591524_v25_n6_p916_Galagovsky
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Galagovsky, Diego Acevedo, Julieta María Sorianello, Eleonora Mariana Wappner, Pablo The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner
topic_facet	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
description	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.
author	Galagovsky, Diego Acevedo, Julieta María Sorianello, Eleonora Mariana Wappner, Pablo
author_facet	Galagovsky, Diego Acevedo, Julieta María Sorianello, Eleonora Mariana Wappner, Pablo
author_sort	Galagovsky, Diego
title	The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner
title_short	The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner
title_full	The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner
title_fullStr	The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner
title_full_unstemmed	The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner
title_sort	drosophila insulin-degrading enzyme restricts growth by modulating the pi3k pathway in a cell-autonomous manner
publishDate	2014
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10591524_v25_n6_p916_Galagovsky http://hdl.handle.net/20.500.12110/paper_10591524_v25_n6_p916_Galagovsky
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The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner

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