A new study clarifies how a mysterious hormone, GDF15, makes insulin work better in rodents.

As reported in Cell Metabolism , the researchers were the first to discover that the hormone GDF15 actually improves sensitivity in mice and rats, making them better suited to regulate their blood sugar and absorb energy in their muscles. The findings increase our general understanding of GDF15 and suggest potential benefits for diabetes and overweight.

“Increased insulin sensitivity is an important indicator of health and critical for avoiding type 2 diabetes, high blood pressure, and cardiovascular diseases. That we are now able to demonstrate a beneficial effect of GDF15 in rodents raises interesting perspectives,” says senior author Erik Richter, a professor at the University of Copenhagen.

Among other things, previous studies demonstrated that the hormone caused obese rodents to lose weight because the hormone acts as an appetite suppressant.

In the current study, the researchers wanted to see if lean rodents benefitted from receiving the GDF15 hormone, even though they did not lose weight. The experiments showed that a low dose of GDF15 every other day, spread over three occasions, improved insulin action.

“Because quite high doses of GDF15 are needed to curb appetite, our lean rodents didn’t lose weight with the low doses that we gave them. However, their insulin sensitivity improved. It turned out that it was primarily their liver and fatty tissue that increased insulin sensitivity, and not the muscles, as we had anticipated,” Richter says.

High insulin sensitivity is a good health indicator because lowered insulin sensitivity—called insulin resistance —strains insulin secretion in the pancreas and can lead to the onset of type 2 diabetes, among other things.

The hormone’s ability to act as an appetite suppressant has also been tested in humans, but caused nausea as a side effect. However, nausea also occurs with other appetite suppressant formulations. Whether GDF15 also increases insulin sensitivity in humans remains to be studied.

The GDF15 stress hormone is not unknown among scientists due to it being secreted in a very diverse range of physiological states. For example, GDF15 concentrations increase during physical activity, with aging, and in people who are overweight or battling serious diseases like cancer or heart disease.

In pregnant women, levels of the hormone are elevated 100 times above normal. The better a person’s physical fitness, the lower their GDF15 levels are in the bloodstream while at rest.

It might be tempting to think of GDF15 as an inverse biomarker of general health—the lower the GDF15 while at rest, the better. But as with all of the other physiological conditions in which this mysterious hormone is in some way involved, the researchers still do not know exactly what role GDF15 plays.

“The hormone stands out because it is secreted in so many different situations without us fully understanding why and what its effect is. On one hand, we can see that it improves insulin sensitivity in mice, which is a positive physiological effect.

“But at the same time, it’s a hormone that increases under various types of stress. How exactly this is all connected is something that we need to investigate more thoroughly,” Richter says.

Source: University of Copenhagen

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