A new Target For Diabetes Therapy-Inceptor (Insulin Inhibitory Receptor)

1. Huateng Pharma https://en.huatengsci.com A new Target For Diabetes Therapy-Inceptor (Insulin Inhibitory Receptor) Diabetes was once an incurable and even fatal disease. Patients could only delay the progression of the disease through strict dietary restrictions, and some patients even died of hunger. Until 1921, Canadian scientist Frederick Banting conducted a series of animal experiments, he discovered and successfully extracted insulin, which was used in clinical practice in 1922. The discovery and application of insulin have saved the lives of a large number of diabetic patients. So far, insulin injection is still the main treatment for diabetic patients. One hundred years later, there is still no drug treatment that can prevent or reverse the progress of diabetes. Popular drugs such as semaglutide can only delay the progress of diabetes. Previous studies have found that intensive insulin therapy may improve blood sugar control and relieve diabetes, but this therapy may also lead to weight gain or more serious side effects, such as an increased risk of patients with a sharp drop in blood sugar, which may be make the patient unconscious. On the 100th anniversary of the discovery of insulin, on January 27, Nature published a milestone study in the field of diabetes. Researchers from the Helmholtz Zentrum Muenchen of the Technical University of Munich, Germany, and the German Diabetes Research Center discovered a new type of drugable insulin inhibitory receptor (named inceptor by the author) that blocks the function of this receptor and results in increased sensitivity of the insulin signaling pathway in pancreatic β-cells. This research focuses on the development of regenerative methods for the treatment of diabetes, which can be used to supplement and replace classic immune and metabolic therapies. The discovered insulin inhibitory receptor (inceptor) is a promising molecular target in β-cell protection and regenerative therapy. Moreover, the use of regenerative therapy will not cause unexpected side effects similar to those caused by insulin intensive therapy. "Insulin resistance of pancreatic islet β-cells can trigger diabetes. Therapies that make β-cells sensitive to insulin may protect diabetics from β-cell loss and failure." said Professor Heiko Lickert, the corresponding author of the paper. Researchers have observed in mouse experiments that the inceptor can inhibit the activation of INSR-IGF1R (INSR: insulin receptor; IGF1R: insulin-like growth factor 1 receptor). It is worth noting that this receptor is up-regulated in diabetes, and it may lead

2. Huateng Pharma https://en.huatengsci.com to insulin resistance by blocking insulin signalling. Inceptors (black) desensitize insulin receptor (color) on pancreatic β-cells, blue is insulin (Source: Helmholtz Zentrum München) The research team tried to inhibit the inceptor from genetic or pharmacological aspects to explore the function of the inceptor. The results showed that the activation of INSR-IGF1R and the proliferation of β-cells increased after the inceptor specificity of β-cells in adult mice and isolated pancreatic islets was knocked out.

3. Huateng Pharma https://en.huatengsci.com After β-cell knockout of inceptor, mice have higher glucose tolerance and β-cell proliferation increased (Source: Nature) In terms of mechanism, the inceptor interacts with INSR-IGF1R to promote clathrin-mediated endocytosis, leading to desensitization of INSR and IGF1R. The researchers used monoclonal antibodies that target the extracellular domain of the receptor to block this physical interaction and maintain the activation of INSR-IGF1R in β-cells. Use monoclonal antibodies to block inceptor function and maintain INSR-IGF1R activation in β-cells (Source: Nature) "The result is exactly what we hope. The number of insulin signals and functional β-cells has increased. This makes the insceptor a very promising target." said Ansarullah, the first author of the paper. "Frederick Banting pointed out in his Nobel Prize-winning speech 100 years ago that

4. Huateng Pharma https://en.huatengsci.com insulin is not a way to treat diabetes, but a way to treat symptoms of diabetes. In the future, our research goal is to develop drugs that can regenerate β-cells based on the discovery of insceptors. Patients with type 1 and type 2 diabetes may benefit from this, and eventually lead to remission of diabetes." Professor Lickert said. As a professional pharmaceutical intermediates, APIs and research chemicals manufacturer in China, Huateng Pharma supplies anti-cancer intermediates, canti-viral intermediates, anti-diabetic intermediates and so on. For anti-diabetic intermediates, there are Semaglutide intermediates and Liraglutide intermediates we are able to provide. References: [1] Ansarullah, Jain, C., Far, F. F. et al. Inceptor counteracts insulin signalling in β-cells to control glycaemia. Nature (2021) [2] Diabetes: Neue Entdeckung könnte die Behandlung künftig verändern(Source: Helmholtz Zentrum München) [3] Louis Rosenfeld. Insulin: Discovery and Controversy. Clinical Chemistry (2002) Related articles: [1] Antidiabetic Drugs Classification and Mechanism of Action [2] Liraglutide, Used For Treating Against Type 2 Diabetes And Obesity [3] The things you need to know about diabetes [4] A Novel Approach Against Type 1 Diabetes [5] Oral Semaglutide : First Oral GLP-1 Treatment for Type 2 Diabetes [6] Glucagon Like Peptide 1 (GLP-1) Agonist Drugs for Type 2 Diabetes