The functions of insulin signaling: size isn't everything, even in Drosophila

Mammalian insulin and insulin-like growth factors (IGFs) signal through several receptors with different ligand specificities to regulate metabolism and growth. This regulation is defective in diabetes and in a wide variety of human tumors. Recent analysis in Drosophila melanogaster has revealed tha...

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Bibliographic Details
Published in:Differentiation (London) 2003-09, Vol.71 (7), p.375-397
Main Authors: Goberdhan, Deborah C.I., Wilson, Clive
Format: Article
Language:English
Subjects:
aging
Animals
Biological and medical sciences
Biotechnology
cancer
Cell Cycle Proteins - physiology
Cell Differentiation
Cell physiology
diabetes
Disease Models, Animal
Drosophila - growth & development
Drosophila - metabolism
Drosophila melanogaster
Endocrine Glands - metabolism
Female
Fundamental and applied biological sciences. Psychology
Gene therapy
growth
Health. Pharmaceutical industry
Humans
Industrial applications and implications. Economical aspects
Insulin - physiology
Macromolecular Substances
Molecular and cellular biology
Nutritional Status
PTEN
Receptor, Insulin - physiology
Signal Transduction
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Summary:Mammalian insulin and insulin-like growth factors (IGFs) signal through several receptors with different ligand specificities to regulate metabolism and growth. This regulation is defective in diabetes and in a wide variety of human tumors. Recent analysis in Drosophila melanogaster has revealed that insulin-like molecules (known as DILPs in flies) also control growth and metabolism, but probably do so by signaling through a single insulin receptor (InR). The intracellular signaling molecules regulated by this receptor are highly evolutionarily conserved. Work in flies has helped to dissect the network of InR-regulated intracellular signaling pathways and identify some of the critical players in these pathways and in interacting signaling cascades. Surprisingly, these studies have shown that DILPs control tissue and body growth primarily by regulating cell growth and cell size. Changes in cell growth produced by these molecules may subsequently modulate the rate of cell proliferation in a cell type-specific fashion. At least part of this growth effect is mediated by two small groups of neurons in the Drosophila brain, which secrete DILPs into the circulatory system at levels that are modulated by nutrition. This signaling center is also involved in DILP-dependent control of the fly's rate of development, fertility, and life span. These surprisingly diverse functions of InR signaling, which appear to be conserved in all higher animals, reflect a central role for this pathway in coordinating development, physiology, and properly proportioned growth of the organism in response to its nutritional state. Studies in flies are providing important new insights into the biology of this system, and the identification of novel components in the InR-regulated signaling cascade is already beginning to inform the development of new therapeutic strategies for insulin-linked diseases in the clinic.
ISSN:0301-4681
1432-0436
DOI:10.1046/j.1432-0436.2003.7107001.x