Diabetes alternative to insulin found in adipose tissue

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Blood sugar levels can be regulated independently of insulin

Around 100 years ago, the discovery of insulin opened the door to the treatment of diabetes. Since then, the hormone produced in the pancreas has been considered the most important means of treating diseases that are characterized by high blood sugar levels. An American research team has now discovered a completely new way of regulating blood sugar without insulin – a second hormone that performs exactly the same function as insulin.

Researchers at the Salk Institute in California (USA) discovered a molecule that is produced in adipose tissue and, like insulin, regulates blood sugar levels quickly and effectively. The discovery could lead to the development of new therapies for the treatment of diabetes and at the same time lay the foundation for new knowledge in metabolic research. The study results were recently presented in the renowned journal ” Cell Metabolism “.

An alternative way of regulating blood sugar levels

According to the working group, a hormone called FGF1 regulates blood sugar by inhibiting fat breakdown (lipolysis). Insulin also inhibits this process, but in a completely different way. The researchers have thus found an alternative way of regulating blood sugar that bypasses insulin resistance.

Breakthrough in metabolic research

“The discovery of a second hormone that suppresses lipolysis and lowers blood sugar levels is a scientific breakthrough,” emphasizes Professor Ronald Evans from the research team. “We have identified a new actor in the regulation of fat burning that will help us understand how energy stores are managed in the body.”

What happens when the body is insulin resistant?

When we eat, high-energy fats and glucose enter the bloodstream. Normally, insulin transports these nutrients to cells in muscles and adipose tissue, where they are either consumed immediately or stored for later use. In people with insulin resistance, glucose is not removed efficiently from the blood, and the increased lipolysis causes fatty acid levels to rise.

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alternative to insulin
alternative to insulin

These additional fatty acids in turn accelerate glucose production in the liver, which further increases the already high glucose level. In addition, the fatty acids accumulate in the organs and worsen insulin resistance, which is characteristic of diabetes and obesity.

FGF1 decreased insulin resistance in mice

In an earlier study, the researchers at the Salk Institute discovered that the hormone FGF1 drastically lowers blood sugar levels in mice. Treatment with the hormone reduced the animals’ insulin resistance. The underlying processes were unclear at the time.

Similarities with insulin

In the current research work, the team succeeded in elucidating the mechanisms behind this phenomenon. The scientists proved that the hormone fulfills functions similar to insulin. On the one hand, FGF1 – just like insulin – suppresses lipolysis. On the other hand, FGF1 regulates the production of glucose in the liver – just like insulin does.

alternative to insulin
alternative to insulinFGF1 uses a different signal path

Due to their similar function, the researchers investigated whether FGF1 and insulin use the same signaling pathways to regulate blood sugar. It is already known that insulin initiates lipolysis through an enzyme called PDE3B. So the team tested this and a number of similar enzymes on FGF1. They discovered that FGF1 uses a completely different signal path called PDE4.

“This mechanism is basically a second loop, with all the advantages of a parallel path,” emphasizes lead study author Gencer Sancar. In the case of insulin resistance, the insulin signaling is disrupted. The resistance can be circumvented with another signal path that fulfills the same functions. In this way, despite resistance, you still have control over lipolysis and blood sugar regulation.

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Hope for better drugs for diabetes

The discovery of the new PDE4 signaling pathway opens up new possibilities for the development of diabetes drugs and at the same time offers numerous starting points for further metabolic studies. “The unique ability of FGF1 to bring about a sustained lowering of blood sugar levels in insulin-resistant diabetic mice is a very promising therapeutic approach for diabetics,” sums up Michael Downes from the research team. (vb)