糖尿病猕猴 z-bo 2020-12-26 331

　　Diabetes Mellitus (DM) is a metabolic disease that seriously endangers human health. It is currently one of the five diseases with the highest morbidity and mortality in the world. In recent years, with the improvement of people's living standards and the gradual increase of population aging, the incidence of diabetes has increased year by year. According to the World Health Organization (WHO), as of 2015, there are 415 million diabetic patients worldwide, and China is the world's largest diabetic country.

　　 A large number of epidemiological data show that obesity is an independent risk factor for the onset of type 2 diabetes, but how obesity causes diabetes is still unknown. At present, most of the research on obesity and type 2 diabetes is constructed by using rodents such as mice and rats, induced by acute high-calorie food, or damaging pancreatic β cells with chemical drugs. However, these unnaturally constructed rodent models often fail to simulate human type 2 diabetes well. In contrast, non-human primates such as macaques (Macaca mulatta) have a genetic background and physiological structure that are closer to humans, and their spontaneous diabetes course and symptoms are more similar to human diabetes. They are very important for studying human type 2 diabetes. Good animal model. Researcher Liang Bin from the Kunming Institute of Zoology, Chinese Academy of Sciences and Liu Pingsheng from the Institute of Biophysics, Chinese Academy of Sciences have conducted large-scale screening of more than 2,000 macaques raised by the Kunming Institute of Zoology after four years, and successfully screened out a batch of spontaneous obesity And spontaneously diabetic macaques; further observation found that the physiological and biochemical indicators of these macaques are very close to human obesity and diabetes. Subsequently, they cooperated with the team of researcher Zhou Hu from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences to conduct proteomics research on spontaneous obesity and diabetic macaque liver. Liver proteomics data analysis and functional experiments show that fatty liver occurs in the liver of spontaneously obese macaques, and fatty acid oxidation pathways and fat synthesis pathways are significantly up-regulated. This phenotype is very different from the mouse model induced by high calories, but it is very similar to the phenotype of human fatty liver. Spontaneous diabetic macaques develop obesity and hyperlipidemia in the early stage, while the body weight and blood lipids in the late stage are reduced, and there is obvious liver damage; liver proteomics shows that the oxidative phosphorylation pathway and branched chain amino acid degradation pathway are significantly up-regulated, and the liver damage may be in the liver Excessive ROS is caused by inducing mitochondria to release cytochrome c and activating Caspase3 in the cytoplasm. This study revealed for the first time that under natural conditions, during the transition from obesity to diabetes, liver energy metabolism changes from fatty acid oxidation to branched chain amino acid degradation, providing a new idea for the pathogenesis of obesity-induced diabetes.