Insulin-inhibitory receptor research offers hope for type 2 diabetes therapy
Key Takeaways
- Research targeting the insulin-inhibitory receptor, or inceptor, unveils promising avenues for beta cell protection, offering hope for causal diabetes therapy.
- Removing inceptor from mice with diet-induced obesity enhances glucose regulation, suggesting it may be a good drug target for type 2 diabetes treatment.
The insulin resistance of beta cells contributes to their dysfunction and the transition from obesity to type 2 diabetes. However, all current pharmacotherapies for type 2 diabetes, including insulin supplementation, focus on managing high blood sugar levels rather than addressing the underlying cause of diabetes: beta cell failure or loss. Therefore, research into beta cell protection and regeneration is crucial and holds promising prospects for addressing the root cause of diabetes, offering potential avenues for causal treatment.
With the recent discovery of the insulin-inhibitory receptor, or inceptor, the research group of beta cell expert Prof. Heiko Lickert has uncovered an interesting molecular target. Lickert and colleagues found that the levels of inceptor are increased in diabetes and may contribute to insulin resistance. Inhibiting the function of inceptor could enhance insulin signaling—which in turn is required for overall beta cell function, survival, and compensation upon stress.
In new research, Lickert and Prof. Timo Müller, an expert in molecular pharmacology in obesity and diabetes, explored the effects of inceptor knock-out (genetic removal of inceptor) in diet-induced obese mice. They found that mice lacking inceptor exhibited improved glucose regulation without experiencing weight loss, which was linked to increased insulin secretion in response to glucose.
Next, they investigated the distribution of inceptor in the central nervous system and discovered its widespread presence in neurons (nerve cells). Deleting inceptor from neuronal cells also improved glucose regulation in obese mice. Ultimately, the researchers selectively removed inceptor from the mice’s beta cells, resulting in enhanced glucose control and a slight increase in beta cell mass. The results were published in Nature Metabolism.
“Our findings support the idea that enhancing insulin sensitivity through targeting inceptor shows promise as a pharmacological intervention, especially concerning the health and function of beta cells,” says Müller. Lickert added, “Since inceptor is expressed on the surface of pancreatic beta cells, it becomes an accessible drug target. Currently, our laboratory is actively researching the potential of several inceptor-blocking drug classes to enhance beta cell health in pre-diabetic and diabetic mice.”
Edited by Miriam Kaplan, PhD
Source: Verena Schulz, Helmholtz Association of German Research Centres, Medical Xpress, February 298, 2024; see source article