Brazilian endocrinologist Décio Eizirik has a special interest in the pancreas. Not only in its role in food digestion by releasing digestive enzymes into the intestines, but also in its use of hormones to finely and dynamically adjust blood levels of glucose, the body’s main energy source. In his 40 years of research, he has described some of the mechanisms that cause pancreatic cells to stop producing insulin, the hormone that helps glucose enter tissue, where it is used as cellular fuel. More recently, Eizirik and his team at Vrije Universiteit Brussel (VUB) in Belgium have begun to discover how exercise can protect the pancreas and help prevent—or at least delay—the development of diabetes.
During physical activity, muscles release compounds that enter the bloodstream, which carries them to other organs. Over the past eight years, Eizirik and colleagues have identified at least three such compounds that help reduce inflammation associated with diabetes and reduce the death of beta cells, which synthesize insulin. The protective effect of the most recently evaluated compound, perhaps the most potent of them, was described in the journal Diabetology in April.
In the study, physiologist José Maria Costa Júnior, who is doing a postdoctoral fellowship at VUB, tested the effect of a molecule called meteorin-like protein (Metrnl) on beta cells cultured under conditions that mimic diabetes. He also evaluated the effect of Metrnl on mini-organs similar to pancreatic islets (clusters of hormone-producing cells) under the same circumstances.
In the past, Eizirik found that in diabetes, inflammatory molecules alter the functioning of beta cells and direct immune cells to destroy them, a phenomenon that is more pronounced in type 1 diabetes. Pretreatment with Metrnl reduced the mortality of beta cells—whether isolated or in mini-organs—by up to 41% in an inflammatory environment that simulated a person with diabetes. Metrnl also preserved the beta cells’ ability to produce and secrete insulin.
A stronger effect was observed when Costa Júnior used a serum from people who had undergone 10 weeks of intense physical exercise instead of a Metrnl solution. The exercise program increased the concentration of Metrnl in the blood by 40%. When used to treat cells and mini-organs, plasma from these volunteers reduced cell death by 46%.
The protection provided by Metrnl disappeared when the scientists added an antibody that neutralizes the protein to the cells and mini-organs. “The result shows that this protein is necessary to produce the protective effect of physical exercise on pancreatic cells,” explains Costa Júnior.
The VUB group knows that other molecules also contribute to the beneficial effect of exercise. “It is certainly not due to the action of just one factor,” says Eizirik. “People with diabetes are therefore likely to benefit more if they learn to exercise systematically and routinely.”
The idea of looking for protective molecules in the blood of people who do physical activity arose almost 15 years ago, when Eizirik worked with biologist Flávia Maria Moura de Paula during her sandwich PhD at the University of Campinas (UNICAMP). Supervised by physiologist Antonio Carlos Boschero, Moura de Paula conducted experiments with serum from rodents undergoing an exercise program, observing that it prevented the death of pancreatic cells in a model of diabetes. The pair then repeated the tests with serum from eight healthy volunteers who underwent physical training in Campinas and confirmed the protective effect, described in the FASEB Journal in 2018. When analyzing the serum components, Moura de Paula found that the impact was partly due to interleukin 6, a protein that in this case had an anti-inflammatory effect.
In a later experiment, biomedical scientist Alexandra de Brachène tested the serum on a larger group of people—82 in total, including healthy individuals, overweight individuals, and people with type 1 or 2 diabetes—who had been separated into three groups, each undergoing a different training program (cycling, running, and functional training) for two months. Again, the serum reduced beta cell mortality by up to 35%, regardless of exercise type and diabetes status, the researchers reported in Diabetologia in 2023. The protective effect was maintained even with serum extracted two months after the training program ended. Brachène obtained similar results by using a solution of clusterin, an anti-inflammatory protein released during exercise, instead of whole serum.
“The results we have obtained so far lead us to believe that Metrnl is responsible for up to half of the protective effect of the serum from individuals doing exercise, since most of the effect disappeared when this protein was blocked,” says Eizirik.
“These experiments suggest that physical exercise helps protect against diabetes via two mechanisms,” explains Sergio Atala Dib, an endocrinologist from the Federal University of São Paulo (UNIFESP) who did not participate in the studies. “The first, already known, is by increasing insulin sensitivity, the efficiency with which the body’s cells respond to this hormone. The second, which is beginning to become evident, is by reducing inflammation and preventing immune cells from attacking the pancreas, which is the cause of type 1 diabetes,” says the researcher, who showed that the modulating effect of vitamin D3 on the immune system helped preserve pancreatic beta cell function in the early stages of type 1 diabetes in a study published in the journal Archives of Pediatrics & Adolescent Medicine in 2012.
The team from Brussels believes that regular exercise could particularly benefit these people, who still maintain some capacity to produce insulin. To verify whether exercise actually slows the progression of the disease, however, a clinical trial needs to follow dozens of people for at least 12 months. “Colleagues from England and Finland are interested in doing just that,” says Eizirik.
The story above was published with the title “Fight diabetes with exercise” in issue 353 of July/2025.
Projects
1. Molecular mechanisms involved in pancreatic beta cell dysfunction and death in diabetes mellitus: Strategies for inhibiting these processes and restoring islet mass (n° 15/12611-0); Grant Mechanism Thematic Project; Principal Investigator Antonio Carlos Boschero (UNICAMP); Investment R$2,693,164.32.
2. Vitamin D3 associated with insulin treatment in newly diagnosed type 1 diabetes mellitus: Th1/Th2 response, behavior of regulatory T lymphocytes, and residual insulin secretion (n° 07/58164-8); Grant Mechanism Regular Research Grant; Principal Investigator Sergio Atala Dib (Unifesp); Investment R$90,672.45.
Scientific articles
COSTA-JUNIOR, J. M. et al. Exercise induced meteorin like protein protects human pancreatic beta cells from cytokine induced apoptosis. Diabetologia. Apr. 12, 2025.
PAULA, F. M. M. et al. Exercise training protects human and rodent endoplasmic reticulum stress and apoptosis. The Faseb Journal. Jan. 3, 2018.
DE BRACHÈNE, A. C. et al. Exercise as a non-pharmacological intervention to protect pancreatic beta cells in individuals with type 1 and type 2 diabetes. Diabetologia. Nov. 19, 2022.
GABBAY, M. A. L. et al. Effect of cholecalciferol as adjunctive therapy with insulin on protective immunologic profile and decline of residual β-cell function in new-onset type 1 diabetes mellitus. Archives of Pediatrics & Adolescent Medicine. July 2012.
