Housekeeping genes regulate brain insulin resistance

  The brain plays an important role in controlling our blood sugar levels. In patients with type 2 diabetes, the brain's control of glucose metabolism is usually dysfunctional. So far, the genetic mechanism behind this phenomenon is still elusive. Recently, Helmholtz Zentrum München and scientists from the German Diabetes Research Center (DZD) published their findings in the Journal of Clinical Research. Genetic mutations in the male DUSP8 gene have been shown to increase the risk of type 2 diabetes by weakening the brain's response to insulin.

  Insulin is a pancreatic hormone that controls our blood sugar levels. Insulin not only stimulates the movement of glucose in the blood to surrounding tissues, but also acts on the brain, especially the hypothalamus, to control glucose and energy metabolism. In obese people, the activation of inflammatory signals in turn impairs the cell response downstream of the insulin receptor, and insulin loses some activity. This phenomenon is called insulin resistance and is the main indicator of the development of type 2 diabetes. The recent genome-wide association study (GWAS) has identified DUSP8 as a risk gene for type 2 diabetes. Subsequently, the scientists studied how the protein Dusp8 (dual specific phosphatase 8) encoded by the DUSP8 gene regulates glucose tolerance and insulin sensitivity. Dr. Sonja C. Schriever explained: “It has been shown that carriers of genetic variants of the DUSP8 gene are at risk of developing type 2 diabetes, but it is not clear how important Dusp8 is in the pathogenesis of the disease. “By combining cell models, Human mice and human functional magnetic resonance imaging (fMRI) with genetic variants of Dusp8 mutant DUSP8 gene have specific effects of Dusp8 protein as a systemic glucose regulator and chest cavity. Reveal the effect of reducing insulin sensitivity.

  Dusp8 protein regulates the inflammatory process of the hypothalamus and hypothalamic-pituitary-adrenal (HPA) axis. Scientists say that removing the Dusp8 gene in male mice will increase inflammation in the female hypothalamus, weaken the HPA axis feedback, and protect the body from insulin activation and insulin sensitivity. Studies have shown that basal stress hormone levels are elevated, all of which increase insulin sensitivity. The sex-specific effect of Dusp8 is consistent with fMRI data from human volunteers. The males of the DUSP82 variant are females.