Open Close
Kim, J., Bilder, D., Neufeld, T.P. (2018). Mechanical stress regulates insulin sensitivity through integrin-dependent control of insulin receptor localization.  Genes Dev. 32(2): 156--164.
FlyBase ID
Publication Type
Research paper

Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the Drosophila larval fat body, an insulin-sensitive organ analogous to vertebrate adipose tissue and livers. We found that insulin signaling in Drosophila fat body cells is abolished in the absence of physical activity and mechanical stress even when excess insulin is present. Physical movement is required for insulin sensitivity in both intact larvae and fat bodies cultured ex vivo. Interestingly, the insulin receptor and other downstream components are recruited to the plasma membrane in response to mechanical stress, and this membrane localization is rapidly lost upon disruption of larval or tissue movement. Sensing of mechanical stimuli is mediated in part by integrins, whose activation is necessary and sufficient for mechanical stress-dependent insulin signaling. Insulin resistance develops naturally during the transition from the active larval stage to the immotile pupal stage, suggesting that regulation of insulin sensitivity by mechanical stress may help coordinate developmental programming with metabolism.

PubMed ID
PubMed Central ID
PMC5830928 (PMC) (EuropePMC)
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Genes Dev.
    Genes & Development
    Publication Year
    Data From Reference
    Alleles (35)
    Genes (31)
    Natural transposons (1)
    Insertions (4)
    Experimental Tools (2)
    Transgenic Constructs (30)