Examine uncovers a novel promising goal for diabetes therapy

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Researchers have discovered a novel and drugable insulin-inhibiting receptor called the Inceptor. The latest study by the Helmholtz Zentrum München, the Technical University of Munich and the German Center for Diabetes Research is an important milestone for diabetes research as science celebrates 100 years of insulin and 50 years of the discovery of insulin receptors.

The blockage of the receptor function leads to an increased sensitization of the insulin signaling pathway in pancreatic beta cells. This could enable the protection and regeneration of beta cells for diabetes remission.

Diabetes mellitus is a complex disease characterized by the loss or dysfunction of insulin-producing beta cells on the islets of Langerhans, a specialized “microorgan” in the pancreas that controls systemic blood sugar levels. Diabetes complications such as chronically high blood sugar, systemic metabolic failure and long-term damage to multiple organs cause enormous medical and social burdens and lead to premature death. Currently, no pharmacological treatment can stop or reverse the progression of the disease.

Previous studies have shown that intensive insulin therapy has the potential for improved blood sugar control and diabetes remission, but it also leads to unintended weight gain and even more serious side effects such as: B. an increased risk of deep blood sugar dripping, which leads to ignorance.

Heiko Lickert’s research focuses on the development of regenerative approaches for the treatment of diabetes, which are complementary and alternative to classical immunological and metabolic therapies.

“Insulin resistance in beta cells in the pancreas causes diabetes. Therapies that make these cells sensitive to insulin can protect patients with diabetes from beta cell loss and failure,” says Lickert.

With the discovery of the insulin-inhibiting receptor, his research group found a promising molecular target for beta-cell protection and regeneration therapy that does not have the unintended side effects of intensive insulin therapy.

In experiments with mice, the researchers showed that the function of the receptor is to protect the insulin-producing beta cells from activating the constitutive insulin pathway. Remarkably, the inceptor is upregulated in diabetes and can contribute to insulin resistance by blocking the insulin signal.

What happens when the function of the inceptor is genetically or pharmacologically inhibited? The group investigated this question by turning off Inceptor in beta cells and blocking its function with monoclonal antibodies.

“The result was exactly what we hoped for: insulin signaling and functional beta cell mass increased. This makes Inceptor a promising target for treating the root cause of diabetes, beta cell loss and dysfunction,” says Ansarullah, the first author of the study, published in the Natur- und Diabetesforscher at Helmholtz Zentrum München.

“Frederick Banting stated in his Nobel Prize lecture for the discovery of the life-saving drug insulin a hundred years ago that ‘Insulin is not a cure for diabetes, it is a treatment for symptoms.’ This has not changed in the last century, our goal for future research is to leverage the discovery of Inceptor and develop drugs for beta cell regeneration, which could be beneficial for patients with type 1 and 2 diabetes and ultimately lead to diabetes remission, “explains Lickert.

A hundred years ago, the discovery of insulin turned a deadly disease into a manageable disease. Our discovery of the insulin-inhibiting receptor is now another important step towards getting rid of the disease for good. While the COVID-19 pandemic is an imminent threat that we will overcome, we must not forget that diabetes remains one of the biggest and fastest growing killers on our planet. With a number of recent breakthroughs, including the discovery of Inceptor, our Helmholtz Diabetes Center is doubling its mission to be a diabetes-free world. “

Matthias Tschöp, CEO, Helmholtz Center Munich

Source:

Helmholtz Zentrum München – German Research Center for Environmental Health

Journal reference:

Ansarullah et al. (2021) Inceptor counteracts the insulin signal in β-cells in order to control glycemia. Nature. doi.org/10.1038/s41586-021-03225-8.