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Sato-Miyata Y, Muramatsu K, Funakoshi M, et al. Overexpression of dilp2 causes nutrient-dependent semi-lethality in Drosophila. Front Physiol. 2014;5:147doi: 10.3389/fphys.2014.00147.
Sato-Miyata, Y., Muramatsu, K., Funakoshi, M., Tsuda, M., & Aigaki, T. (2014). Overexpression of dilp2 causes nutrient-dependent semi-lethality in Drosophila. Frontiers in physiology, 5147. https://doi.org/10.3389/fphys.2014.00147
Sato-Miyata, Yukiko, et al. "Overexpression of dilp2 causes nutrient-dependent semi-lethality in Drosophila." Frontiers in physiology vol. 5 (2014): 147. doi: https://doi.org/10.3389/fphys.2014.00147
Sato-Miyata Y, Muramatsu K, Funakoshi M, Tsuda M, Aigaki T. Overexpression of dilp2 causes nutrient-dependent semi-lethality in Drosophila. Front Physiol. 2014 Apr 16;5:147. doi: 10.3389/fphys.2014.00147. eCollection 2014. PMID: 24795642; PMCID: PMC3997005.
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Front Physiol. 2014 Apr 16;5:147. doi: 10.3389/fphys.2014.00147. eCollection 2014.

Overexpression of dilp2 causes nutrient-dependent semi-lethality in Drosophila.

Frontiers in physiology

Yukiko Sato-Miyata, Keigo Muramatsu, Masabumi Funakoshi, Manabu Tsuda, Toshiro Aigaki

Affiliations

  1. Cellular Genetics Laboratory, Department of Biological Sciences, Tokyo Metropolitan University Tokyo, Japan.
  2. Department of Liberal Arts and Human Development, Faculty of Health and Social Services, Kanagawa University of Human Services Yokosuka, Japan.

PMID: 24795642 PMCID: PMC3997005 DOI: 10.3389/fphys.2014.00147

Abstract

Insulin/insulin-like growth factor (IGF) plays an important role as a systemic regulator of metabolism in multicellular organisms. Hyperinsulinemia, a high level of blood insulin, is often associated with impaired physiological conditions such as hypoglycemia, insulin resistance, and diabetes. However, due to the complex pathophysiology of hyperinsulinemia, the causative role of excess insulin/IGF signaling has remained elusive. To investigate the biological effects of a high level of insulin in metabolic homeostasis and physiology, we generated flies overexpressing Drosophila insulin-like peptide 2 (Dilp2), which has the highest potential of promoting tissue growth among the Ilp genes in Drosophila. In this model, a UAS-Dilp2 transgene was overexpressed under control of sd-Gal4 that drives expression predominantly in developing imaginal wing discs. Overexpression of Dilp2 caused semi-lethality, which was partially suppressed by mutations in the insulin receptor (InR) or Akt1, suggesting that dilp2-induced semi-lethality is mediated by the PI3K/Akt1 signaling. We found that dilp2-overexpressing flies exhibited intensive autophagy in fat body cells. Interestingly, the dilp2-induced autophagy as well as the semi-lethality was partially rescued by increasing the protein content relative to glucose in the media. Our results suggest that excess insulin/IGF signaling impairs the physiology of animals, which can be ameliorated by controlling the nutritional balance between proteins and carbohydrates, at least in flies.

Keywords: Drosophila insulin-like peptides; autophagy; growth regulation; hyperinsulinemia; insulin-like growth factor signaling; protein-to-carbohydrate ratio

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