Hepatic PTPR-γ may be a target for treatment of type 2 diabetes
Obesity, which is defined as a body mass index of 30 or greater, has become a major global health challenge. The worldwide prevalence of obesity has increased significantly in recent several decades. A wide range of health complications associated with obesity has been established. One common complication of obesity is type 2 diabetes.
Type 2 diabetes is also called adult-onset diabetes because the disease is predominantly found in adults. The increased levels of obesity have led to an increase in type 2 diabetes among young people. Type 2 diabetes is the most common form of diabetes and is characterized by high blood sugar, insulin resistance, and relative lack of insulin.
Previous studies have suggested that inflammation induced by obesity contributes to insulin resistance and type 2 diabetes. For instance, inflammation-related molecules increased in obesity, such as LTB4, IL-1β, and TNF-α, appear to have an impact on insulin function. These molecules may act via the NF-κB signaling pathway, which seems to be implicated in the induction of insulin resistance. Until now, however, the precise mechanisms remain incompletely understood.
Now, a study titled "Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance," which was published online in Nature Communications, provided new clues to the link between obesity-induced inflammation and insulin resistance involved in type 2 diabetes. Senior author of the study, Roberto Coppari from the University of Geneva in Switzerland, pointed out that they mainly studied a protein called PTPR-γ
, which is a target of NF-kβ.
PTPR-γ, short for Protein Tyrosine Phosphatase Receptor Gamma, is a member of the protein tyrosine phosphatase (PTP) family. The role of PTPR-γ in cellular metabolism remains unknown. There is evidence that PTPR-γ is upregulated during inflammation.
For the current study, Coppari's team found that PTPR-γ was upregulated in the context of obesity and inflammation in mice and it correlated with inflammation and insulin resistance in humans. A high-caloric-diet has been established to induce inflammation, obesity, and diabetes in mice. In mice totally lacking PTPR-γ, the researchers found that a high-caloric-diet caused the animals to develop obesity but it did not trigger insulin resistance or diabetes. This suggested that PTPR-γ deficiency had a protective role against the development of insulin resistance.
When the researchers re-expressed PTPR-γ in the liver of mice lacking PTPR-γ, they found that the animals became susceptible to hepatic and systemic insulin resistance. The results indicated the increased hepatic PTPR-γ level observed in obesity could cause insulin resistance. Therefore, hepatic PTPR-γ might be a novel target for treatment of type 2 diabetes.
In conclusion, the study identifies hepatic PTPR-γ as an important link between obesity-induced inflammation and insulin resistance. Inhibition of PTPR-γ function represents a potential therapeutic strategy for type 2 diabetes.
In addition to the University of Geneva, researchers from Gunma University in Japan and New York University Langone School of Medicine in the USA also participated in the study.