Exercise hormone protects kidneys from damage caused by diabetes

Researchers at the State University of Campinas conducted experiments on rats and human kidney cells. Their findings, published in Scientific Reports, show that irisin, a hormone secreted in muscle tissue during exercise, avoids the cellular degeneration that leads to diabetic nephropathy and kidney failure.

By Mônica Tarantino  |  Agência FAPESP – Irisin is a hormone secreted by muscle tissue during exercise. Scientists have discovered that it can protect the kidneys of people with diabetes from the damage caused as the disease progresses. Known as the “exercise hormone”, it is considered one of the key chemical messengers responsible for the many health benefits of regular physical activity. 

In a study that included a run of experiments, researchers at the State University of Campinas (UNICAMP) in Brazil not only confirmed the benefits of irisin for the kidneys but also described for the first time how it can prevent damage to them from diabetes. Kidney disease is silent and affects 20%-40% of diabetics. Diabetes damages the blood vessels that irrigate the kidneys, leading to chronic kidney failure.

“We found that aerobic exercise is associated with an increase in muscle irisin in the bloodstream and the kidneys, conferring nephroprotection,” said physician José Butori Lopes de Faria, professor of nephrology at the university’s School of Medical Sciences (FCM-UNICAMP) and head of its Laboratory of Renal Pathophysiology and Investigation of Diabetes Mellitus Complications. 

Faria supervised the PhD research of Guilherme Pedron Formigari, first author of an article published in Scientific Reports with the results of the study, which was supported by FAPESP. 

According to Brazilian Ministry of Health data for 2021, the prevalence of diabetes in the adult population of Brazil is 9.14%, corresponding to more than 15 million people. Brazil ranks sixth among countries with the most cases of diabetes, as reported by the International Diabetes Federation (IDF) in its 2021 atlas, which also states that diabetes caused 6.7 million deaths worldwide in 2021. The World Health Organization and IDF established November 14 as World Diabetes Day in 1991 to raise awareness and encourage prevention of a disease that affects over 400 million adults internationally. 

Methodology

The researchers began the study by inducing diabetes in rats aged eight weeks and measuring their kidney functions via indicators such as urine albumin. Any amount of albumin in the urine is a sign that a diabetic patient’s kidneys are starting to underperform owing to the disease. 

The rats were divided into three groups: a non-diabetic control group, a sedentary diabetic group and a diabetic group submitted to an exercise training protocol on a treadmill for eight weeks.

“We found aerobic exercise to be associated with increased irisin levels in muscle tissue and in the bloodstream, and with an increase in the enzyme AMPK [adenosine monophosphate-activated protein kinase, a central regulator of energy homeostasis] in the kidneys, conferring nephroprotection,” Faria said.

The researchers then injected drugs into the diabetic rats submitted to the exercise protocol to block the action of irisin in the kidneys. This removed the beneficial effects of exercise, such as a reduced level of urine albumin and lower levels of substances involved in glomerular filtration. The absence of irisin canceled out the protective effects of exercise on the diabetic kidneys, according to the article.

Another experiment involving human kidney tubule cells cultured in the laboratory was performed to find out whether treatment with irisin would be capable of avoiding alterations such as high blood sugar. During filtration in the kidneys, the tubules reabsorb water, electrolytes and required nutrients by transferring them out of the filtrate and returning them to the bloodstream. In the experiment, they were immersed in a medium that mimicked the conditions of diabetes and contained recombinant irisin supplied by a pharmaceutical firm. 

“The response was positive,” Faria said. “We concluded that exercise increases muscle and blood irisin levels and that the presence of the hormone in the kidneys activates AMPK, which blocks the mechanisms of renal fibrosis [one of the main causes of chronic kidney disease].”

Previous research by Faria, also supported by FAPESP, demonstrated the role of AMPK in renal fibrosis, a consequence of chronic inflammation of kidney cells, which become unable to function properly.

In the latest study, the researchers analyzed human serum (the clear liquid part of the blood that remains after centrifugation to remove red blood cells and clotting proteins) from sedentary diabetics and diabetics submitted to exercise training. In the samples from the physically active group, the presence of irisin protected the kidneys and mitigated the damage to tubules exposed to high blood sugar.

“This result allows us to suggest, to the best of our knowledge for the first time, that in diabetes the irisin/AMPK axis may mediate the kidney protection induced by physical exercise,” the authors write in the article. 

Irisin was discovered by biologists at Harvard University a decade ago and many studies have since been conducted to understand its action mechanism. One study, for example, shows that irisin is important to memory formation and neuron protection in mice with a disease similar to Alzheimer’s.

The article “Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy” is at: www.nature.com/articles/s41598-022-13054-y.