Overweight increases the risk of an imbalance in sugar metabolism and even of diabetes. A research group has now shown the opposite is true as well: deficits in the body’s insulin production contribute to overweight.

Poor nutrition, too little movement and too many pounds on the scale – lifestyle influences the risk of metabolic diseases like diabetes. But the relationship works the other way round as well, as a research group reports. If insulin production is compromised, as is the case in the early stages of type 2 diabetes, this can contribute to overweight. The researchers report their findings in the journal Nature Communications.

The research team focused on protease PC1/3, a key enzyme in the body that transforms various inactive hormone precursors into the final, active forms. If this enzyme isn’t functioning properly in a person, the result can be severe endocrine disorders. The consequences include a feeling of uncontrollable hunger and severe overweight.

“Until now, it was assumed that this dysregulation is caused by a lack of activation of satiety hormones,” explains the study's leader. “But when we turned off PC1/3 in the brains of mice, the animals’ body weight did not change significantly.” The researchers concluded from this that something other than a brain malfunction must be responsible.

In their next step, they tested whether overweight could be caused by incorrect activation of other hormones. PC1/3 activates insulin, among other things. Insulin plays a key role in the regulation of blood sugar and fat metabolism. “Investigating the role of insulin production as a cause of overweight was obvious,” says the lead. The researchers shut off PC1/3 specifically in the insulin-producing beta cells of the pancreas in mice. The animals consumed significantly more calories and soon became overweight and diabetic.

“These results are also interesting because PC1/3 is reduced in the pancreas of patients with prediabetes,” says the senior author of the study. This indicates that incorrect insulin activation could be not only a consequence, but also a cause of overweight.

But PC1/3 is also important in the weight regulation of healthy individuals, the author emphasizes. The researchers were able to show that the gene expression of PC1/3 in the pancreas is negatively correlated with body weight in the general population – meaning that sufficient PC1/3 promotes a healthy body weight.

The finding that a defect in the insulin-producing beta cells is a trigger of overweight opens up new therapeutic possibilities. For example, it is conceivable that medications could be used to reduce the production of immature insulin precursors, creating a new tool in the fight against overweight and diabetes.

https://www.nature.com/articles/s41467-022-32509-4

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fprohormone-convertase-1&filter=22