By Maryna Mullerman ’20

Reduced insulin-like signaling (IIS) can lead to diabetes and damage of neuronal function in metabolism. However, chronically lowered insulin/insulin-like growth factor (IGF) may improve neurodegenerative disease defects. Hrvoje Augustin and researchers at University College London analyzed the escape response mechanism of the fly Drosophila melanogaster and the effects of genetically weakened insulin signaling on this model. This was done to explore the impact of reduced insulin conditions on human cell cultures.

The researchers explored the aging fly’s escape behavior, the transmission of electrical signals in the giant fiber system (GFS). They analyzed the density of electrical synapses from gap-junction (GJ) proteins encoded by transmembrane SHAK-B proteins in Drosophila. To stimulate the GFS, a light air-puff was directed to the fly’s head, and the nervous system’s response was recorded. After multiple experiments on aging flies, the study proceeded to investigate the effects of lowered IIS on lysosome trafficking using human epithelial cells and acute insulin stimulation.   

The researchers found that lowered IIS improved electrical transmission in again GFS. Moreover, the silencing of ISS in neurons conserved GFS function. Even though it was found that the SHAK-B transcription was not affected by lowered IIS, the deficiency of SHAK-B resulted in delays in aging of Drosophila. The experiment with human epithelial cells showed that reducing IIS boosted the formation of gap junction (GJ) proteins in cells by triggering their recycling process to the plasma membrane, and lowered GJ transportation and degradation in the lysosome.

The researchers suggested that reduced insulin signaling has a positive effect on aging flies, enhancing “youthful” response to environmental stimuli. The study provided a new cellular mechanism in which lowered IIS levels could maintain electrical transmission and potentially prevent neuronal decline. The study was only conducted on aging flies and was limited to one type of human cell culture, but the results could potentially be applied to preventive medicine and healthcare. The researchers encourage future insulin studies to be insightful while being circuit– and synapse type– specific, and they suggest that studies should avoid simple generalizations about the function and performance of IIS.

References:

1. H. Augustin, et. al, Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies. PLOS Biology 15, (2017). doi: e2001655.
2. Image retrieved from: https://www.scientificamerican.com/sciam/cache/file/0D3D6C6F-3218-4125-A5764135043AB961_source.jpg