Exercise curbs insulin production

Insulin is an essential hormone for humans and many other living organisms. Its best-known task is probably to regulate sugar metabolism. How it does this job is well researched. Much less is known about how the activity of insulin-producing cells and consequently the release of insulin is controlled.

A team from the Biocentre of Julius-Maximilians-Universität (JMU) Würzburg has now presented new findings on this question in the journal Current Biology. Dr Jan Ache's group used the fruit fly Drosophila melanogaster as a study subject. Interestingly, this fly also secretes insulin after a meal, but in this case the hormone does not come from the pancreas as in humans, but from nerve cells in the brain.

Electrophysiological measurements in active flies

The JMU group has discovered that physical activity in flies has a strong effect on their insulin-producing cells. For the first time, the researchers measured the activity of these cells electrophysiologically in running or flying Drosophila.

Result: When Drosophila starts to run or fly, its insulin-producing cells are inhibited very quickly. When the fly stops its movements, the activity of the cells immediately increases again and at times even shoots above the normal value.

„We assume that the low activity of the insulin-producing cells during exercise contributes to the supply of sugar to meet the increased energy demand," says Dr Sander Liessem, first author of the publication. „And we hypothesise that the increased activity after the cessation of exercise helps to replenish the fly's energy stores, for example in the muscles.“

Blood sugar plays no role in regulation

The JMU team was also able to prove this: The very rapid behaviour-dependent inhibition of insulin-producing cells is actively controlled by neural pathways. It is largely independent of changes in the sugar concentration in the animals' blood," explains co-author Dr Martina Held.

It makes a lot of sense for the organism to anticipate an increasing energy requirement in this way in order to prevent extreme fluctuations in the blood sugar level.

Insulin has hardly changed in the course of evolution

Do the results allow conclusions to be drawn about humans? Probably yes.

„Although the secretion of insulin in fruit flies takes place via different cells than in humans, the insulin molecule and its function have hardly changed over the course of evolution,

says Jan Ache. And over the past 20 years, many fundamental questions have already been answered using Drosophila as a model organism, which could also contribute to a better understanding of metabolic defects in humans and the associated diseases such as diabetes or obesity.

Less insulin means longevity

„An exciting point is that reduced insulin activity contributes to healthy ageing and longevity,

says Sander Liessem. This has already been proven in flies, mice, humans and other species. The same applies to an active lifestyle.

Our work shows a possible connection here as to how physical activity could have a positive effect on insulin regulation via neuronal signalling pathways.

Further steps in the research

The next step for Jan Ache's team is to investigate which messenger substances and nervous system circuits are responsible for the change in activity of the insulin-producing cells in the fly. This should be challenging: Several messenger substances are usually involved in neuromodulation processes, and the individual substances can have opposing or complementary effects in combination.

The group is now analysing the various ways in which insulin-producing cells receive input from the outside. They are also investigating other factors that could influence the activity of these cells, such as the age of the flies or their nutritional status.

„At the same time, we are investigating the neuronal control of walking behaviour,

explains Jan Ache. The long-term goal of his group is to bring these two research questions together: How does the brain control running and other behaviours, and how does it ensure that the energy balance is regulated accordingly?

Promotion

The German Research Foundation (DFG) is supporting Jan Ache's group as part of the Emmy Noether and Neuronex programmes. Both funding instruments have contributed significantly to the success of this work.

Source: Press release Julius-Maximilians-Universität Würzburg from 04 January 2023