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How does the body regulate the activity of insulin-producing cells in order to react quickly to changing conditions? Researchers at the University of Würzburg have investigated this question.
The hormone insulin plays a central role in the metabolism of many living organisms. When food is plentiful, insulin promotes the absorption and storage of energy. In times of hunger, however, insulin secretion is reduced; the body conserves energy or searches for alternative energy sources. It is crucial for survival that this system is finely tuned. If it gets out of balance, there is a risk of diabetes and other metabolic diseases.
Humans produce insulin in their pancreas. In the fruit fly Drosophila, however, the hormone is produced by nerve cells located on the brain. These cells release the insulin directly into the haemolymph - the fluid that fulfils the functions of blood in insects. Apart from this, however, the insulin system of the fly is very similar to that of humans.
Published in the Journal eLife
Scientists at Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, have now taken a closer look at the insulin-producing cells of the fruit fly. They aimed to unravel how these cells in the fly's brain work together with other neurons to produce a concerted response to metabolic demands and internal state changes.
The results have been published in the scientific journal eLife. Dr Jan Ache, head of an Emmy Noether group at the Department of Neurobiology and Genetics at the JMU Biocentre, is responsible for the study.
Tracking the Activity of Individual Cells
How do insulin-producing cells (IPC) in living insects react to changes in energy balance? Little is known about this so far. To close this knowledge gap, Jan Ache's team used an approach that allows recording the activity of individual IPCs in living fruit flies under different conditions.
They found that the IPCs release insulin when the flies ingest sugar with their food - but not when sugar is injected directly into the haemolymph.
‘In humans, this phenomenon is known as the incretin effect,’ explains Jan Ache. It suggests that insulin secretion is not simply controlled by the rise in blood sugar levels, but by more complex mechanisms involving gut hormones.
The JMU team also found that IPC activity is much lower in older flies. It is therefore possible that the way in which the insects process sugar changes with age – similar to humans.
Influence on Foraging Behaviour Investigated
The foraging behaviour of fruit flies is closely linked to fluctuations in their energy reserves, which in turn are linked to insulin secretion. The Würzburg team also wanted to find out more about these relationships.
The researchers therefore stimulated the IPCs optogenetically – mimicking what normally happens after a meal and a rise in sugar levels. It turned out that the insulin-producing cells play only a minor role in modulating foraging behaviour compared to other nerve cells.
Studies May be Relevant for Humans
‘With our experiments, we have refined our knowledge of the circuits that control insulin secretion in fruit flies,’ says Jan Ache. This now enables further investigations, which could ultimately lead to findings that are relevant to human health and diseases such as diabetes. Although humans and fruit flies are very different in appearance, they have some similarities in their genetics and metabolism, including the function of the nervous system and core aspects of metabolic regulation.
Dr Jan Ache, Emmy Noether Junior Research Group for Neuronal Mechanisms of Context-dependent, Flexible Behavioural Control, University of Würzburg, T +49 931 31-88577, jan.ache@uni-wuerzburg.de
Nutritional state-dependent modulation of insulin-producing cells in Drosophila. Rituja S. Bisen, Fathima Mukthar Iqbal, Federico Cascino-Milani, Till Bockemühl, Jan M. Ache. eLife, 29 January 2025, Open Access https://doi.org/10.7554/eLife.98514.3
The image shows in magenta the insulin-producing cells (IPCs) and a second group of nerve cells (DH4 ...
Rituja Bisen
University of Wuerzburg
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The image shows in magenta the insulin-producing cells (IPCs) and a second group of nerve cells (DH4 ...
Rituja Bisen
University of Wuerzburg
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