Being overweight makes you more likely to have a sugar metabolism problem or even get diabetes. The contrary is also true, as recently demonstrated by a study team at the University of Basel: deficits in the body’s insulin production cause obesity.

Lifestyle factors including poor nutrition, insufficient exercise, and excess weight on the scale affect the risk of metabolic illnesses like diabetes. But as a research team led by Dr. Daniel Zeman-Meier of the university’s Department of Biomedicine and the University Hospital of Basel explains, the relationship also works the other way around.

Impaired insulin production, which happens in type 2 diabetes in its early stages, can cause obesity.

The findings are published in the journal Nature Communications.

When hormones don’t work right

The research team concentrated on protease PC1/3, a crucial enzyme that converts inactive hormone precursors into their final, active forms. If this enzyme is not working properly in a person, severe endocrine problems may follow. The results include extreme overweight and an overwhelming sense of hunger.

“Until now,” according to the study’s leader, Dr. Zeman-Meier, “it was assumed that this dysregulation is caused by a lack of activation of satiety hormones. 

But when they “turned off PC1/3 in the brains of mice, the animals’ body weight did not change significantly.” 

This led the researchers to believe that something other than a brain dysfunction must be to blame.

Incorrect insulin activation results in hunger and obesity.

The researchers then investigated whether improper hormone activation could contribute to obesity. Among other things, insulin is activated by PC1/3. The regulation of blood sugar and fat metabolism is greatly influenced by insulin. According to Dr. Zeman-Meier, investigating the role of insulin production as a contributor to obesity was evident. In the pancreas of mice, the researchers deliberately turned down PC1/3 in the insulin-producing beta cells. The animals ate a lot more calories, which led to their rapid weight gain and the development of diabetes.

A key part of the human body

Professor Marc Donath, the head of the research group and the study’s third author, notes that this study’s findings are also intriguing because prediabetic patients’ pancreases had lower levels of PC1/3, which is a marker of the disease. This suggests that improper insulin activation may lead to weight gain as well as be a contributing factor.

Donath notes that PC1/3 is crucial for maintaining appropriate weight in healthy people as well. The researchers were able to demonstrate that the expression of the PC1/3 gene in the pancreas is negatively linked with average body weight, indicating that having enough PC1/3 encourages a healthy body weight.

The discovery that obesity is caused by a malfunction in the beta cells that produce insulin opens up new treatment avenues. In the fight against obesity and diabetes, for instance, it is feasible that drugs could be used to decrease the production of immature insulin precursors.

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