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JCI: Scientists discover potential ways to treat early type 2 diabetes

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Recently, in a research report published in the International Journal of Clinical Investigation, researchers from the Sanford Burnham Prebys Institute of Medical Discovery have identified a potential drug target that inhibits the occurrence of type 2 diabetes. The results show that , Blocking the glucose receptors in the cells of muscle may improve the body’s responsiveness to insulin.

Researcher Dr. Daniel P. Kelly said that our findings have found that a protein called MondoA may act as a key link between insulin resistance and fat accumulation in muscles, which often occurs in obesity-related diabetic patients. In this study, for the first time, this study tested the efficacy of MondoA targeted drugs in inhibiting type 2 diabetes in preclinical trials. Approximately 8% of Americans have type 2 diabetes, and 25% of the population is at risk of diabetes due to obesity. Type 2 diabetes is a lifelong disease that brings a great burden to public health. Treatment 2 The cost of type diabetes accounts for 20% of all medical expenses in the United States. At the same time, the treatment of diabetes complications will cost a large part of the medical expenses, including kidney, peripheral nerve and retinal damage.

The precursor of type 2 diabetes is insulin resistance, that is, insulin cannot promote the body’s cells to absorb glucose from the diet and use it as energy; and this often leads to diabetes, because glucose will continue to circulate in the blood and stimulate the pancreas to produce More insulin, which eventually causes the insulin-producing cells to be overloaded and die. In this study, the researcher Kelly’s research focused on skeletal muscle, because skeletal muscle is the main insulin-responsive tissue in the body; the early marker of insulin resistance is the accumulation of fat in the muscle, which is accompanied by glucose input. Therefore, the researcher wants to determine whether these two processes are related through research and analysis. In order to find proteins that regulate the above two processes, researchers screened thousands of molecules to find protein molecules that can block fat synthesis and enhance glucose uptake in muscle cells.

The researchers said that SBI-477 is the best molecule we have screened. Through the investigation of the cell effect of SBI-477, we have discovered the protein MondoA; relevant experimental results show that the protein can regulate the special features involved in fat synthesis and inhibit insulin signaling. Gene expression. So far, researchers do not know why insulin-resistant individuals accumulate fat in the muscle tissue of the body, but the results of this article show that MondoA is the mechanism that links these phenomena, and it can be used as a guard to fuel the muscle cells. Speed up the combustion.

After further research, the researchers found that SBI-477 can also enhance the uptake of glucose by liver cells, which indicates that MondoA blockers may have similar effects on a variety of tissues. From a deeper level, MondoA may alleviate Insulin tolerance of mice on a high-fat diet. Researcher Kelly believes that under normal circumstances, the protein MondoA can respond to oversupply of glucose by inhibiting glucose from entering cells and enhancing its conversion into fat, but continuous activation often promotes the development of insulin resistance.

In the next step, the researcher Kelly and colleagues plan to develop special molecules that can better inhibit MondoA. Finally, the researchers pointed out that directly enhancing the uptake of glucose by muscles and other tissues may be a new strategy for developing anti-diabetic drugs, because this process is very needed. The burning of energy functions, so it may have a beneficial effect on the body’s overall metabolism and weight control.

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