Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling
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Specific neurosecretory cells of the Drosophila brain express insulin-like peptides (dilps), which regulate growth, glucose homeostasis, and aging. Through microarray analysis of flies in which the insulin-producing cells (IPCs) were ablated, we identified a target gene, target of brain insulin (tobi), that encodes an evolutionarily conserved alpha-glucosidase. Flies with lowered tobi levels are viable, whereas tobi overexpression causes severe growth defects and a decrease in body glycogen. Interestingly, tobi expression is increased by dietary protein and decreased by dietary sugar. This pattern is reminiscent of mammalian glucagon secretion, which is increased by protein intake and decreased by sugar intake, suggesting that tobi is regulated by a glucagon analog. tobi expression is also eliminated upon ablation of neuroendocrine cells that produce adipokinetic hormone (AKH), an analog of glucagon. tobi is thus a target of the insulin- and glucagon-like signaling system that responds oppositely to dietary protein and sugar.
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In Drosophila, the ablation of insulin-producing cells of fed flies increased the expression of a lysosomal α-mannosidase in concurrence with a down-regulation of an evolutionary conserved α-glucosidase-target of brain insulin (tobi)-whose overexpression reduces body glycogen.
“For instance, in Drosophila, the ablation of insulin-producing cells of fed flies increased the expression of a lysosomal α-mannosidase in concurrence with a down-regulation of an evolutionary conserved α-glucosidase—target of brain insulin (tobi) (66)—whose overexpression reduces body glycogen.”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [66]
In flies and humans, changes in expression and activity levels of α-mannosidases have been linked to impairments in insulin signaling and glucose metabolism.
“In both flies and humans, changes in expression and activity levels of α-mannosidases have been linked to impairments in insulin signaling and glucose metabolism (66–70).”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [66]
Both AKH peptide in flies and vertebrate glucagon can elicit increased glucose production by both glycogenolysis and gluconeogenesis.
“Both of these can elicit increased glucose production by both glycogenolysis and gluconeogenesis.”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [66]
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- Authors
- Buch, S., Melcher, C., Bauer, M., Katzenberger, J., & Pankratz, M. J.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Corresponding author
- Pankratz, Michael J.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 7
- Issue
- 4
- Pages
- 321-332
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2074304856
- Cited by
- 179
- References
- 44
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 14 · 2020: 19 · 2019: 10 · 2018: 12 · 2017: 10 · 2016: 15 · 2015: 14 · 2014: 13 · 2013: 7 · 2012: 8
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Publication Server of Bonn-Rhein-Sieg University of Applied Sciences (Bonn-Rhein-Sieg University of Applied Sciences) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- alpha-glucosidase, adipokinetic hormone, dietary protein, dietary sugar, insulin-producing cells, neuroendocrine cells, growth defects, glucose homeostasis, Drosophila
- MeSH terms
- alpha-Glucosidases, Animals, Dietary Carbohydrates, Dietary Proteins, Drosophila, Enzyme Activation, Fat Body, Female, Insect Hormones, Larva, Longevity, Male, Neurosecretory Systems, Oligopeptides, Pyrrolidonecarboxylic Acid, Somatomedins, Signal Transduction, Gene Expression Regulation, Enzymologic, Drosophila Proteins, RNA Interference, Forkhead Transcription Factors
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