Physiology Fridays: A feeding frenzy–Insulin signalling in larval brains

Insulin is perhaps best known as the crucial molecule whose lack leads to diabetes.  It’s a hormone that regulates carbohydrate and fat metabolism, and signals cells to increase uptake of glucose from the blood.  What most people don’t know is that insects use insulin too.

“Insulin signalling is a very conserved pathway which has been investigated extensively in humans as well as more recently in Drosophila melanogaster,” says Dr. Ana Campos, a researcher in the Biology Department at McMaster University.

And it turns out that in both insects and humans, insulin plays a much broader role in the brain than previously thought.  In a recent paper Dr. Campos and her technician Xiao Li Zhao published in the Journal of Experimental Biology, they showed that insulin signalling in the mushroom body (a critical region of the insect brain) regulates feeding behaviour in fruitfly (Drosophila melanogaster) larvae.

“Insulin has been implicated in a wide variety of biological processes. Its importance goes beyond its well-known role in the regulation of carbohydrate and fat metabolism, says Dr. Campos.  “In addition, it has been implicated in synaptic plasticity and cognitive function in humans and relevant animal models.  Recent findings indicate that abnormal insulin levels contribute to the development of neurodegenerative diseases.”

Image: Mushroom body in D. melanogaster (from Jennett et al. 2006, BMC Bioinformatics, doi:10.1186/1471-2105-7-544)

Investigating the role of insulin signalling in the mushroom body came about by a chance observation in their lab: they found a mutation in the Ran-binding protein M gene (RanBPM) that disrupted feeding behaviour in D. melanogaster larvae also inhibited insulin signalling.  Since this gene is also highly expressed in the mushroom body, it made sense to the researchers to investigate how the mushroom body influenced feeding behaviour and whether insulin signalling mediated it.

The researchers created a series of D. melanogaster strains with different parts of the known insulin-signalling pathway knocked out.  Then they measured the amount of food eaten by the different strains of mutant larvae as well as their resultant growth. By using immunohistochemical labelling, they also were able to find that reduced insulin signalling in the mushroom body on reduced the total number of neurons produced in the brains of these larvae.

Taken together, Dr. Campos and Xiao Li suggest their results mean that the mushroom body could be the brain region responsible for collecting signals about nutritional status in insects, and helps regulate feeding behaviour.  More broadly, this contributes to the knowledge about how insulin signalling impacts brain function.

Zhao, X. L. and Campos, A.R. (2012) Insulin signalling in mushroom body neurons regulates feeding behaviour in Drosophila larvae. J. Exp. Biol. http://www.ncbi.nlm.nih.gov/pubmed/22786647

Keywords: Physiology Fridays, Mushroom body, Insulin, Drosophila melanogaster, research blogging

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