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Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster
Insulin signaling is critical for developmental growth and adult homeostasis, yet the downstream regulators of this signaling pathway are not completely understood. Using the model organism Drosophila melanogaster, we took a genomic approach to identify novel mediators of insulin signaling. These st...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718763/ https://www.ncbi.nlm.nih.gov/pubmed/32998936 http://dx.doi.org/10.1534/g3.120.401688 |
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author | Pereira, Matthew T. Brock, Katia Musselman, Laura Palanker |
author_facet | Pereira, Matthew T. Brock, Katia Musselman, Laura Palanker |
author_sort | Pereira, Matthew T. |
collection | PubMed |
description | Insulin signaling is critical for developmental growth and adult homeostasis, yet the downstream regulators of this signaling pathway are not completely understood. Using the model organism Drosophila melanogaster, we took a genomic approach to identify novel mediators of insulin signaling. These studies led to the identification of Meep, encoded by the gene CG32335. Expression of this gene is both insulin receptor- and diet-dependent. We found that Meep was specifically required in the developing fat body to tolerate a high-sugar diet (HSD). Meep is not essential on a control diet, but when reared on an HSD, knockdown of meep causes hyperglycemia, reduced growth, developmental delay, pupal lethality, and reduced longevity. These phenotypes stem in part from Meep’s role in promoting insulin sensitivity and protein stability. This work suggests a critical role for protein homeostasis in development during overnutrition. Because Meep is conserved and obesity-associated in mammals, future studies on Meep may help to understand the role of proteostasis in insulin-resistant type 2 diabetes. |
format | Online Article Text |
id | pubmed-7718763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-77187632020-12-17 Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster Pereira, Matthew T. Brock, Katia Musselman, Laura Palanker G3 (Bethesda) Investigations Insulin signaling is critical for developmental growth and adult homeostasis, yet the downstream regulators of this signaling pathway are not completely understood. Using the model organism Drosophila melanogaster, we took a genomic approach to identify novel mediators of insulin signaling. These studies led to the identification of Meep, encoded by the gene CG32335. Expression of this gene is both insulin receptor- and diet-dependent. We found that Meep was specifically required in the developing fat body to tolerate a high-sugar diet (HSD). Meep is not essential on a control diet, but when reared on an HSD, knockdown of meep causes hyperglycemia, reduced growth, developmental delay, pupal lethality, and reduced longevity. These phenotypes stem in part from Meep’s role in promoting insulin sensitivity and protein stability. This work suggests a critical role for protein homeostasis in development during overnutrition. Because Meep is conserved and obesity-associated in mammals, future studies on Meep may help to understand the role of proteostasis in insulin-resistant type 2 diabetes. Genetics Society of America 2020-09-30 /pmc/articles/PMC7718763/ /pubmed/32998936 http://dx.doi.org/10.1534/g3.120.401688 Text en Copyright © 2020 Pereira et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Pereira, Matthew T. Brock, Katia Musselman, Laura Palanker Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster |
title | Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster |
title_full | Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster |
title_fullStr | Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster |
title_full_unstemmed | Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster |
title_short | Meep, a Novel Regulator of Insulin Signaling, Supports Development and Insulin Sensitivity via Maintenance of Protein Homeostasis in Drosophila melanogaster |
title_sort | meep, a novel regulator of insulin signaling, supports development and insulin sensitivity via maintenance of protein homeostasis in drosophila melanogaster |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718763/ https://www.ncbi.nlm.nih.gov/pubmed/32998936 http://dx.doi.org/10.1534/g3.120.401688 |
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