Scientists from the German Center for Diabetes Research (DZD) recently investigated how the brain regulates the occurrence of diabetes mellitus. The organ plays an important role in controlling blood sugar levels.For type 2 diabetesHowever, this regulation of glucose metabolism is often disturbed. A group of researchers has now shown that a genetic variant of the DUSP8 gene may increase the risk of juvenile type 2 diabetes mellitus in men. This happens because the gene affects the brain's response to the hormone insulin.
Juvenile diabetes mellitus and glucose tolerance
The genetic factors behind this phenomenon have so far been difficult to explain. However, the research group at the Helmholtz Center Munich and the German Center for Diabetes Research have shown with their results that this can increase the risk of type 2 diabetes. Insulin is a pancreatic hormone that controls blood sugar levels. It not only stimulates the uptake of glucose from the blood into peripheral tissues, but also acts on the brain. This is particularly true in the hypothalamus, where it regulates glucose and energy metabolism. However, in obese individuals, insulin loses some of its activity due to activation of inflammation and subsequent impairment of cellular response downstream of the insulin receptor. This phenomenon, called insulin resistance, is an important hallmark in the development ofType 2 diabetes and possible treatment.
Recent studies identified the DUSP8 gene as a risk factor for the development of diabetes mellitusTyp 2. Now the scientists have investigated how the protein Dusp8 (dual specificity phosphatase 8), encoded by the DUSP8 gene, regulates glucose tolerance and insulin sensitivity. Research has shown that carriers of a genetic variant of the DUSP8 gene have a moderately increased risk of type 2 diabetes. However, the functional significance of Dusp8 in the etiology of the disease remained unknown. This explained Dr. Sonja C. Schriever, the study's lead author. By combining cell models, laboratory mice with loss and gain of function, and functional magnetic resonance imaging (fMRI) of people with genetic variants in the DUSP8 gene, the team has now discovered a specific role for the protein Dusp8 as a protective factor.
New insights
The protein Dusp8 has a regulatory effect on inflammatory processes in the hypothalamus. It appears to protect the organism from overactivation of anti-inflammatory signals and impaired insulin sensitivity in the hypothalamus. The scientists were able to show that eliminating the Dusp8 gene increased hypothalamic inflammation in male, but not female, mice. The basal stress hormone levels also increased, which increased overall insulin sensitivity. The sex-specific role of murine Dusp8 was consistent with fMRI data in human volunteers. These showed reduced hypothalamic insulin sensitivity in male, but not in female, carriers of the DUSP8 risk variant for diabetes mellitus. The elucidation of these multisystem processes in the mouse models was an important step towards understanding the mechanistic basis of the gene. The authorsof the studyIn the future, we plan to further research the effects of insulin and the gene in people with or without type 2 diabetes mellitus.
