In 2021, a research team led by Prof. Heiko Lickert from Helmholtz Munich discovered the insulin-inhibitory receptor "Inceptor" and its role as a suppressor of the insulin signaling pathway. Now, the researchers have unlocked another, even more significant function of the receptor: it binds insulin and directs its breakdown within beta cells. This discovery could lead to new therapeutic approaches that not only strengthen beta cell function but also enable a causal treatment for diabetes.

Prof. Heiko Lickert is the director of the Institute of Diabetes and Regeneration Research at Helmholtz Munich, professor at the Technical University of Munich (TUM), and member of the German Center for Diabetes Research (DZD). Together with his team, they discovered Inceptor in 2021 and described its role as an inhibitor of the insulin signaling pathway. Both Inceptor and the insulin receptor are located on the surface of beta cells, where Inceptor can block the insulin receptor, thus reducing the cells’ insulin sensitivity and weakening the signaling pathway. The current study goes further, showing that Inceptor binds excess insulin within the beta cell and directs it towards degradation. “This knowledge about Inceptor’s function gives us a deeper understanding of how beta cells regulate their insulin homeostasis,” says Heiko Lickert.

Regeneration of Damaged Beta Cells

The increased presence of Inceptor in beta cells suggests that the receptor plays a role in insulin secretion, which is regulated by beta cells. This process is often impaired in diabetes, leading to elevated blood sugar levels. By blocking Inceptor, the researchers were able to refill beta cells' insulin stores, enhance insulin release, and prevent beta cell death. “Especially in already damaged cells, blocking Inceptor could help boost insulin production and protect the beta cells,” explains Lickert.
 

Inceptor proteins moving from within a cell to its surface in a rat insulinoma cell, tagged with a fluorescent marker.  © Lickert/HMGU
 

Hope for People with Type 2 Diabetes

The findings suggest that specifically targeting Inceptor could be a promising strategy for improving the function of insulin-producing cells in people with diabetes. “Our goal is to develop new medications that support the cells’ insulin balance and prolong their viability, based on our discovery”" says Lickert. Such a therapy could especially help individuals in the early stages of type 2 diabetes to slow disease progression and reduce the risk of complications.

From Lab to Practice: A Start-up for New Diabetes Therapies

To translate these findings from the lab to real-world applications, Lickert founded the start-up Viacure together with Dr. Nikolas Uez. Both founders share the vision of advancing the development of drugs that specifically block Inceptor to protect or regenerate beta cells. Preclinical studies to test the safety and efficacy of these innovative therapeutic approaches are a crucial step on this path. “Our shared goal is to pave the way for clinical trials and thereby make a significant contribution to the treatment, and hopefully even the cure, of diabetes,” Lickert and Uez explain.

Original publication:
Siehler et al. (2024): Inceptor binds to and directs insulin towards lysosomal degradation in β-cells. Nature Metabolism. DOI: 10.1038/s42255-024-01164-y.

Scientific contact:
Prof. Dr. Heiko Lickert
Head of the Institute of Diabetes and Regeneration Reseach
Helmholtz Munich
Phone: +49 (0)89 3187-3760
E-Mail: heiko.lickert(at)helmholtz-munich.de

Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies and chronic lung diseases. With the power of artificial intelligence and bioengineering, the researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en    

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Munich – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of Helmholtz Munich at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en