Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction

The neuroendocrine architecture and insulin/insulin-like signaling (IIS) events in Drosophila are remarkably conserved. As IIS pathway governs growth and development, metabolism, reproduction, stress response, and longevity; temporal, spatial, and nutrient regulation of dilps encoding Drosophila ins...

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Main Authors:	Kannan, Kavitha, Fridell, Yih-Woei C.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797364/

id	pubmed-3797364
recordtype	oai_dc
spelling	pubmed-37973642013-10-17 Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction Kannan, Kavitha Fridell, Yih-Woei C. Physiology The neuroendocrine architecture and insulin/insulin-like signaling (IIS) events in Drosophila are remarkably conserved. As IIS pathway governs growth and development, metabolism, reproduction, stress response, and longevity; temporal, spatial, and nutrient regulation of dilps encoding Drosophila insulin-like peptides (DILPs) provides potential mechanisms in modulating IIS. Of eight DILPs (DILP1–8) identified, recent studies have furthered our understanding of physiological roles of DILP2, DILP3, DILP5, and DILP6 in metabolism, aging, and responses to dietary restriction (DR), which will be the focus of this review. While the DILP producing IPCs of the brain secrete DILP2, 3, and 5, fat body produces DILP6. Identification of factors that influence dilp expression and DILP secretion has provided insight into the intricate regulatory mechanisms underlying transcriptional regulation of those genes and the activity of each peptide. Studies involving loss-of-function dilp mutations have defined the roles of DILP2 and DILP6 in carbohydrate and lipid metabolism, respectively. While DILP3 has been implicated to modulate lipid metabolism, a metabolic role for DILP5 is yet to be determined. Loss of dilp2 or adult fat body specific expression of dilp6 has been shown to extend lifespan, establishing their roles in longevity regulation. The exact role of DILP3 in aging awaits further clarification. While DILP5 has been shown associated with DR-mediated lifespan extension, contradictory evidence that precludes a direct involvement of DILP5 in DR exists. This review highlights recent findings on the importance of conserved DILPs in metabolic homeostasis, DR, and aging, providing strong evidence for the use of DILPs in modeling metabolic disorders such as diabetes and hyperinsulinemia in the fly that could further our understanding of the underlying processes and identify therapeutic strategies to treat them. Frontiers Media S.A. 2013-10-16 /pmc/articles/PMC3797364/ /pubmed/24137131 http://dx.doi.org/10.3389/fphys.2013.00288 Text en Copyright © 2013 Kannan and Fridell. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kannan, Kavitha Fridell, Yih-Woei C.
spellingShingle	Kannan, Kavitha Fridell, Yih-Woei C. Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction
author_facet	Kannan, Kavitha Fridell, Yih-Woei C.
author_sort	Kannan, Kavitha
title	Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction
title_short	Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction
title_full	Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction
title_fullStr	Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction
title_full_unstemmed	Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction
title_sort	functional implications of drosophila insulin-like peptides in metabolism, aging, and dietary restriction
description	The neuroendocrine architecture and insulin/insulin-like signaling (IIS) events in Drosophila are remarkably conserved. As IIS pathway governs growth and development, metabolism, reproduction, stress response, and longevity; temporal, spatial, and nutrient regulation of dilps encoding Drosophila insulin-like peptides (DILPs) provides potential mechanisms in modulating IIS. Of eight DILPs (DILP1–8) identified, recent studies have furthered our understanding of physiological roles of DILP2, DILP3, DILP5, and DILP6 in metabolism, aging, and responses to dietary restriction (DR), which will be the focus of this review. While the DILP producing IPCs of the brain secrete DILP2, 3, and 5, fat body produces DILP6. Identification of factors that influence dilp expression and DILP secretion has provided insight into the intricate regulatory mechanisms underlying transcriptional regulation of those genes and the activity of each peptide. Studies involving loss-of-function dilp mutations have defined the roles of DILP2 and DILP6 in carbohydrate and lipid metabolism, respectively. While DILP3 has been implicated to modulate lipid metabolism, a metabolic role for DILP5 is yet to be determined. Loss of dilp2 or adult fat body specific expression of dilp6 has been shown to extend lifespan, establishing their roles in longevity regulation. The exact role of DILP3 in aging awaits further clarification. While DILP5 has been shown associated with DR-mediated lifespan extension, contradictory evidence that precludes a direct involvement of DILP5 in DR exists. This review highlights recent findings on the importance of conserved DILPs in metabolic homeostasis, DR, and aging, providing strong evidence for the use of DILPs in modeling metabolic disorders such as diabetes and hyperinsulinemia in the fly that could further our understanding of the underlying processes and identify therapeutic strategies to treat them.
publisher	Frontiers Media S.A.
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797364/
_version_	1612018468679319552

Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction

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