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Diet and lifestyle

Researchers surprised – exercise can reduce insulin sensitivity

Danish research shows, very surprisingly, that exercise in some cases does not increase insulin sensitivity but reduces it. This discovery may affect how people with diabetes should exercise.

The fact that exercise increases insulin sensitivity in the body and provides accompanying beneficial health effects has long been considered an indisputable fact.

However, this may need to be modified somewhat after Danish researchers recently discovered that a single intense bout of one-legged exercise can actually reduce insulin sensitivity in the rest of the body.

This discovery may affect people with type 1 or type 2 diabetes because they may need to be advised differently on how to exercise in relation to diabetes.

“For many years, researchers have been interested in how physical activity improves health, partly because exercise increases insulin sensitivity in the muscles. Now we have shown, very surprisingly, that this may depend on the type of exercise, the intensity and/or the duration. For example, cycling increases insulin sensitivity in the whole body, whereas exercising a few muscle groups intensively in the gym can actually reduce insulin sensitivity in the rest of the body,” explains Jørgen Wojtaszewski, Professor of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen.

The study has been published in Diabetes.

People with diabetes might adjust their exercise routine

Commenting on the new study, Per Bendix Jeppesen, Associate Professor, Department of Clinical Medicine, Aarhus University, says: “Observing that the body increases insulin sensitivity in the working muscles while simultaneously decreasing insulin sensitivity in the resting muscles is incredibly exciting.”

Per Bendix Jeppesen was not involved in the new study, but he has read the article and carries out research on how exercise affects insulin sensitivity.

He has achieved great results in experiments with high-intensity interval training for people with type 2 diabetes.

“This is an exciting study that indicates some mechanisms in the body we did not previously know. This implies that we might need to recommend that people with type 2 diabetes exercise a little differently. Riding a bicycle may be fine because we know that this can increase insulin sensitivity, but exercising the arms and abdomen may further increase this effect so they do not become insulin resistant,” says Per Bendix Jeppesen.

Physical activity increases insulin sensitivity

As more and more people worldwide struggle with diabetes or severe obesity, interest has increased in the body’s health-promoting signalling pathways.

Health-promoting insulin sensitivity, in which the muscles are sensitive to insulin and therefore take up glucose from the blood, is one function that researchers and also the pharmaceutical industry really want to understand.

Research has repeatedly found, for example, that cycling markedly increases insulin sensitivity in the muscles that have performed the work, and this can result in the whole body showing increased insulin sensitivity for up to 2 days after each exercise session.

This is one reason why people with diabetes especially should exercise because it directly reduces their elevated blood glucose and their need for medication.

“We want to determine which mechanisms and signalling pathways are involved. The goal could be to make a pill that can have the same effect as physical activity on insulin sensitivity. After only a few days of inactivity, the insulin sensitivity of muscles and the body as a whole declines substantially,” says Jørgen Wojtaszewski.

Exercise reduces insulin sensitivity in the rest of the body

In the new study, published in Diabetes, Jørgen Wojtaszewski and colleagues asked eight test subjects to perform 2.5 hours of one-legged exercise under controlled laboratory conditions.

The purpose was to exercise the leg to exhaustion.

Then the researchers measured the insulin sensitivity in the muscles of both the active and the inactive legs.

After 4 hours, the insulin sensitivity of the muscles in the leg that had been active was, as expected, higher than that in the inactive leg.

Surprisingly, however, the inactive muscles had lower insulin sensitivity than they did on a complete day of rest.

“When muscles perform physical work, they often consume large amounts of glycogen. Our body has evolved so that the muscles that need to replenish their fuel depots after a session of physical activity adapt such that they primarily benefit from the available glucose in the blood. This is achieved by increasing the insulin sensitivity of the muscles so that insulin is much more effective. We understood this intuitively, but we were greatly surprised that insulin sensitivity declined in the rest of the body. No one had observed this before, but this effect naturally only helps to increase the availability of glucose for the muscles that need to replenish their glucose reserves after physical activity,” explains Jørgen Wojtaszewski.

The researchers became aware of this phenomenon in a previous study. However, the study had a different purpose and could therefore not answer the question correctly.

“In fact, some of our initial results were laughed at because they contradicted long-held beliefs. We therefore decided to set up a new study designed to answer this one question. The study showed the same result. It really surprised us that exercise may result in making the whole body insulin resistant,” says Jørgen Wojtaszewski.

Incorporating the results into the relationship between diabetes and exercise

Jørgen Wojtaszewski believes that the implications of the new study are interesting, even though the experiments were carried out in the laboratory and involved a fairly extreme form of physical activity.

People with type 1 diabetes often struggle to manage it, and for many, the fluctuation in blood glucose caused by physical activity is another complex factor to consider.

This is probably one reason why many people with type 1 diabetes are not physically active, even if they would benefit from it.

“The problem is that people treated with insulin have to adjust their dose according to their body's needs. If they take too much insulin, they can experience hypoglycaemia and can lose consciousness and eventually die. If the body’s insulin needs depend on whether you have been active and the type of activity, then these factors need to be considered in daily life and medication,” explains Jørgen Wojtaszewski.

Vital for insulin therapy

Jørgen Wojtaszewski explains that future studies will shed light on how different types of physical activity influence insulin sensitivity and insulin resistance in the whole body or parts of it.

In the future, people with type 1 diabetes could well administer their insulin in one way on days when they go running and in another way on days when they lift weights.

In addition, different methods of exercising can affect different individuals differently. All of this needs to be incorporated into the algorithms people with diabetes use to dose their insulin.

“These results can clearly be useful in clinical practice. In the past, we insisted that exercise makes people more insulin sensitive, but now we can see that the situation is more nuanced, and this has implications for people with type 1 or type 2 diabetes,” says Jørgen Wojtaszewski.

A single bout of one-legged exercise to local exhaustion decreases insulin action in non-exercised muscle leading to decreased whole-body insulin action” has been published in Diabetes. In 2016, the Novo Nordisk Foundation awarded a grant to Jørgen Wojtaszewski for the project Exercising with Muscle Insulin Sensitivity.

Jørgen Wojtaszewski
Professor
Our research focus on the mechanism(s) by which physical activity promotes metabolic health. Our studies have focused on the role of the energy sensor AMP activated protein kinase in promoting adaptations to exercise training and to a single bout of exercise. Of particular interest for now more than 20 years have been the interaction at the intracellular level between exercise-induced signaling events and those induced by insulin trying to elucidate the mechanisms by which a single bout of exercise can improve muscle insulin sensitivity. Our approaches to gain such insights include invasive studies of healthy and diseased subjects in combination with mechanistic studies using animal models - including various transgenic approaches. We seek to adapt state of art technologies in our research - including metabolomics, proteomics and phosphoproteomics analyses. Further, we seek to gain insight at the single muscle fiber level using both biochemistry and imaging techniques. In collaborations with various clinical laboratories and pharma industries we aim to translate our findings into relevance for patients and society.