Inceptor counteracts insulin signalling in β-cells to control glycaemia
A team of researchers from Helmholtz Zentrum München, the Technical University of Munich, and the German Center for Diabetes Research has made a groundbreaking discovery in the field of diabetes treatment. They have identified a new insulin inhibitory receptor, named inceptor, which plays an important role in regulating insulin signaling in pancreatic beta cells. This discovery could pave the way for innovative therapies aimed at protecting and regenerating beta cells, offering new hope for diabetes patients.
Understanding Inceptor and Its Role
Diabetes mellitus is a complex disease marked by the loss or dysfunction of insulin-producing beta cells in the pancreas. These cells are crucial for regulating blood sugar levels, and their failure can lead to chronic high blood sugar, systemic metabolic failure, and long-term complications. The newly identified inceptor helps shield beta cells from constant activation of the insulin signaling pathway. This regulation is essential for maintaining beta cell function and preventing their uncontrolled growth, which is a significant factor in the progression of diabetes.
Experimental Findings
In their experiments with mice, the researchers explored the effects of inhibiting inceptor function both genetically and pharmacologically. They used genetic techniques to knock out inceptor in beta cells and employed monoclonal antibodies to block its function. The results were remarkable: insulin signaling increased, and the functional mass of beta cells was enhanced. These findings suggest that targeting inceptor could protect beta cells from failure and potentially regenerate them, addressing the root cause of diabetes rather than just managing its symptoms.
Mice lacking inceptor showed increased insulin receptor (INSR) and insulin-like growth factor 1 receptor (IGF1R) activation in pancreatic tissue, which led to greater beta cell proliferation and mass. This increased activity improved glucose tolerance, demonstrating the potential of inceptor inhibition to enhance beta cell function. Furthermore, the researchers observed that blocking the interaction between inceptor and INSR–IGF1R kept these receptors at the cell surface, sustaining their activation and promoting beta cell growth.
Implications for Diabetes Treatment
This discovery is particularly significant as it offers a potential alternative to intensive insulin therapy. While insulin therapy is effective in controlling blood sugar, it often leads to unintended side effects such as weight gain and severe hypoglycemia. By focusing on inceptor as a therapeutic target, researchers aim to develop treatments that can sensitize beta cells to insulin without these adverse effects.
Current diabetes treatments primarily manage the symptoms of the disease but do not address the underlying causes. Inceptor inhibition represents a shift towards therapies that could protect and regenerate beta cells, offering a more comprehensive approach to diabetes management. This strategy could be especially beneficial for patients with both type 1 and type 2 diabetes, who experience beta cell loss and dysfunction.
Future Research and Goals
The discovery of inceptor opens new avenues for diabetes research. The researchers hope to leverage this finding to develop drugs that can regenerate beta cells and ultimately achieve diabetes remission. This approach could transform the treatment landscape, moving beyond symptom management to address the disease's root causes.
Dr. Heiko Lickert, a leading researcher in this study, emphasizes the importance of this discovery. While insulin therapy has managed diabetes symptoms for the past century, it has not provided a cure. The goal now is to move beyond symptom management to address the underlying causes of diabetes through beta cell regeneration. The research team's work shows promise for developing therapies that can protect and regenerate beta cells, potentially leading to long-term remission of the disease.
A Step Toward a World Without Diabetes
Matthias Tschöp, CEO at Helmholtz Zentrum München, highlights the broader impact of this research. Despite the immediate threat of the COVID-19 pandemic, diabetes remains one of the fastest-growing and most deadly diseases worldwide. The discovery of inceptor is a critical step towards reducing the global burden of diabetes and ultimately eradicating the disease.
In conclusion, the identification of the insulin inhibitory receptor, inceptor, marks a significant milestone in diabetes research. By targeting this receptor, new therapies could emerge that protect and regenerate insulin-producing beta cells, offering a promising path towards diabetes remission and a future free from this debilitating disease.
Citation: Ansarullah, Yu, L., Wei, Y., Arteaga, C. A. P., Sakurai, M., Schmitz, D. A., Zheng, C., Ballard, E. D., Tschöp, M., & Lickert, H. (2021). Resistance to insulin and insulin-like growth factor 1 (IGF1) in pancreatic β-cells causes overt diabetes in mice; thus, therapies that sensitize β-cells to insulin may protect patients with diabetes against β-cell failure. Cell Stem Cell. DOI: 10.1016/j.stem.2021.03.011