糖尿病,肥胖,基因突变 z-bo 2020-09-19 350

　　With age, almost everyone will gain weight, but some people may think that their genes have more fat. Recently, researchers from Duke University in the United States and the Hong Kong University of Science and Technology in China discovered that two different mutations in the ankyrin B gene cause cells to absorb glucose at a faster rate, thereby producing body fat and ultimately leading to obesity. Diabetes has been shown to be a related cause.

　　Nearly one million Americans have a more serious mutation called R1788W. Another mild mutation called L1622I is shared by 7% of African Americans and is a common feature such as sickle red anemia. These findings were produced in mice and help identify people at risk of obesity, who can reverse this situation by improving their diet and strengthening exercise. The relevant research results were published in the internationally renowned academic journal "Journal of Clinical Research" on July 13.

　　The senior author of this article, Van Bennett, professor of biochemistry, cell biology and neurobiology at Duke University School of Medicine, pointed out: "This study is the first to prove that susceptibility genes can only be discovered through modern lifestyles. Obesity must have existed in the 1980s. Popular. At that time, sugar-sweetened soda and fried potatoes were very popular. It seems that it did not suddenly change genes in the 1980s, but this new diet has worsened the susceptibility genes we have. The results of this study are just the beginning , For example, I think there are many genes."

　　Bennett is also a researcher at the Howard Hughes Medical Institute and discovered Ankirin B (Ankirin B) more than 30 years ago. .. He discovered that Anquilin B acts as a protein anchor, connecting important proteins to the cell’s progenitor cell membrane. Since its discovery, Bennett and other researchers have found that Ankyrin B deficiency is associated with various human diseases such as arrhythmia, autism, muscular dystrophy and aging, and more recently diabetes. I found. As people around the world increase waist circumference, diabetes is quickly becoming one of the biggest threats to public health. By 2050, as current trends continue to develop, one-third of Americans will develop diabetes. People with type 1 diabetes cannot produce enough insulin. Insulin is a hormone that helps process glucose that accumulates in the blood after meals. Type 2 diabetic patients with obesity-related diabetes may produce insulin that is resistant to its effects.

　　A few years ago, Bennett's laboratory found evidence that ankyrin B mutation may play a role in insulin secretion and metabolism. Since then, several studies have discovered a rare variant of Anquilin B associated with type 2 diabetes. One mutation is called R1788W and is more common in Caucasian and Hispanic strains. Another mutation, called L1622I, is only found in African Americans who are known to be at a particularly high risk of developing diabetes. However, it is not clear how these genetic code changes lead to diabetes. To solve this problem, Bennett's graduate student Jane Healy prepared mouse models with these same human genetic variants. She and her colleagues found that mice with two variants of r1788w produced less insulin than normal mice. Despite this defect, blood sugar levels are normal. Therefore, the researchers conducted a commonly used sugar tolerance test. It is commonly used to screen patients with type 2 diabetes to determine how the blood levels of mutant mice are cleared. Surprisingly, mutant mice have higher glucose metabolism than normal mice.

　　Healy: "Initially, we thought that the main problem in these mice was the beta cells that produce and secrete insulin. On the contrary, the most important finding was that the target cells far exceeded expectations."

　　If you are completely dependent on yourself, then glucose cannot enter cells or tissues, and instead depends on another molecule called GLUT4 transporter. ".. Usually, GLU T4 hangs outside the cell, just like the hostess is waiting for guests to arrive. When insulin is insufficient, it acts as a doorbell to remind GLUT4 and allow GLUT4 to work and open the door to allow glucose to enter the cell. Insulin consumption After exhaustion, the GLUT4 transporter will close the door and reverse the direction back to the center of the cell.

　　But postdoctoral fellow Damaris Lorenzo discovered that this is not the case in mutant mice. After some biochemical experiments, Lorenzo found that even in the absence of insulin, there is still a large amount of GLUT4 on the surface of mouse muscles and fat cells, which means that glucose can enter the blood without pushing the doorbell.

　　When young, this open-ended strategy is advantageous because it protects animals from low insulin levels. However, as the mice grow older, especially when they switch to a high-fat diet, they will become fatter and eventually develop insulin resistance.

　　Researchers have long believed that the R1788W variant and the mild L1622I may provide evolutionary benefits. The aging hunting type cannot find the next meal very efficiently and should consume as much fat as possible to avoid hunger. Today, the world is rich in high-fat and high-calorie foods, and these variants increase the risk of people suffering from modern diseases such as obesity and diabetes. Lorenzo, the first author of this article, said: "If the carriers of these mutations can be detected early, they can choose personalized interventions, which include not only managing insufficient insulin secretion, but also normal diet and active lifestyle. I think We can avoid metabolic disorders that can seriously affect the quality of life."

　　Next, the researchers studied whether the effects observed in mice affect humans. I think they will study the genotypes of the general population to find families with ankyrin mutations, and conduct family history and glucose metabolism tests to assess the impact of these genetic mutations on the cellular level.