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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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_10591524_v25_n6_p916_Galagovsky |
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todo:paper_10591524_v25_n6_p916_Galagovsky2023-10-03T16:01:02Z The Drosophila insulin-degrading enzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner Galagovsky, D. Katz, M.J. Acevedo, J.M. Sorianello, E. Glavic, A. Wappner, P. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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 |
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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, 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 |
| 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. |
| format |
JOUR |
| author |
Galagovsky, D. Katz, M.J. Acevedo, J.M. Sorianello, E. Glavic, A. Wappner, P. |
| author_facet |
Galagovsky, D. Katz, M.J. Acevedo, J.M. Sorianello, E. Glavic, A. Wappner, P. |
| author_sort |
Galagovsky, D. |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_10591524_v25_n6_p916_Galagovsky |
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