Ⅱ型糖尿病,脂肪肝 z-bo 2020-09-18 312

　　Researchers at Yale University have developed a controlled-release oral therapy that can reverse type 2 diabetes and fatty liver disease in rats.

　　Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are a major factor in the pathogenesis of type 2 diabetes, and none of the existing treatment methods can successfully treat the root causes of these diseases. The research team led by Gerald I. Shulman, Professor of Medicine, Cellular and Molecular Physiology at Yale University School of Medicine, based on previous studies, decided to investigate whether a drug originally used for weight loss more than 70 years ago can be used in rodents with these diseases. Safely treat NAFLD/NASH and type 2 diabetes in the model.

　　According to early research, researchers determined that the toxicity of the drug, the mitochondrial proton carrier (protonophore) 2,4-dinitrophenol (DNP), is related to its peak plasma concentration. They found that a plasma DNP concentration more than 100 times lower than the toxic level can be used to achieve its curative effect in reducing fatty liver and liver inflammation.

　　Shulman is also a researcher at the Howard Hughes Medical Institute. He pointed out: "In addition to reversing fatty liver disease in rodent models of NALFD, a small dose of DNP gavage (100 times less than the toxic level) can also significantly reduce NALFD and 2 Blood glucose, triglyceride and insulin concentrations in rodent models of type 2 diabetes."

　　In the next study, Shulman and his team developed a new oral controlled-release form of DNP, called CRMP, which can keep the drug concentration below the toxicity threshold by more than 100 times. Taken once a day, CRMP produced similar positive effects, reversing fatty liver, insulin resistance and hyperglycemia in NAFLD and type 2 diabetic rat models, as well as liver inflammation and liver fibrosis in NASH animal models without adverse effects.

　　Shulman said: “In view of the gratifying results obtained in NAFLD/NASH and type 2 diabetes animal models, we are further conducting preclinical safety studies to bring this mitochondrial proton carrier method to clinics.”