High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo
| Autor: | Pierre Léopold, Matthieu Pasco |
|---|---|
| Přispěvatelé: | Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Anatomy and Physiology
MESH: Drosophila medicine.medical_treatment Gene Expression lcsh:Medicine 0302 clinical medicine Dietary Sucrose Pleiotropy Drosophila Proteins MESH: Animals Receptor lcsh:Science [SDV.BDD]Life Sciences [q-bio]/Development Biology Genetics 0303 health sciences Multidisciplinary biology Drosophila Melanogaster Animal Models Lipocalins MESH: Insulin Resistance Larva Drosophila MESH: Lipocalins Drosophila melanogaster Drosophila Protein Research Article MESH: Drosophila Proteins Endocrine System Carbohydrate metabolism MESH: Dietary Sucrose Molecular Genetics 03 medical and health sciences Model Organisms Insulin resistance medicine Animals Biology 030304 developmental biology Diabetic Endocrinology Endocrine Physiology Insulin lcsh:R biology.organism_classification medicine.disease lcsh:Q Gene Function Insulin Resistance Animal Genetics MESH: Larva 030217 neurology & neurosurgery Homeostasis Developmental Biology |
| Zdroj: | PLoS ONE, Vol 7, Iss 5, p e36583 (2012) PLoS ONE PLoS ONE, Public Library of Science, 2012, 7 (5), pp.e36583. ⟨10.1371/journal.pone.0036583⟩ |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0036583⟩ |
| Popis: | International audience; In multicellular organisms, insulin/IGF signaling (IIS) plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD) that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D) patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz), a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome. |
| Databáze: | OpenAIRE |
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