So far, this has only been demonstrated in mice, but the research shows that the underlying processes are conserved in humans.
It’s too early to really determine, but a new study shows a pathway to reversing type-2 diabetes and liver fibrosis. So far, this has only been demonstrated in mice, but the research shows that the underlying processes are conserved in humans.
The study comes from a team of researchers at Yale University. The data from the study has been published in Cell Reports and in Nature Communications. In the announcement, the researchers found a connection between the body’s response to fasting and type-2 diabetes. According to the researchers, fasting will begin a process to increase the production of two proteins in the liver. The proteins, TET3 and HNF4a, increase the production of blood glucose. The research showed that in the mice with type-2 diabetes that fasting “switch” fails to turn off when the fasting ends.
The Yale team believed that if they could lower the levels of these two proteins, then it could be possible to prevent type-2 diabetes from developing. The team injected mice with small interfering RNAs (siRNAs) packaged inside viruses that targeted TET3 or HNF4a. When this was done, the team, led by Yingqun Huang, an associate professor in Obstetrics, Gynecology, and Reproductive Sciences, saw significant decreases in blood glucose and insulin. In other words, diabetes was effectively stopped.
When it came to liver fibrosis, the team examined how TET3 contributed to the development of fibrosis in the liver. The research revealed that the protein was involved in fibrosis on multiple levels. Almost all fibrosis, regardless of the organ involved, starts from abnormal protein signaling, Huang said in a statement. Huang and her colleagues saw that TET3 plays a role in the fibrosis signaling pathway in three different locations, and also acts as an important regulator in the development of fibrosis. Da Li, an associate research scientist in genetics and co-author on both studies, suggested that these findings show that there are more opportunities in developing TET3 inhibitors that can slow or reverse fibrosis.
Huang has filed for a patent related to her discoveries with support from the Yale Office of Cooperative Research. For Huang and her team, the next step will be identifying where to best target TET3 and HNF4a and to develop the most effective siRNAs or small molecules to treat type-2 diabetes or fibrosis, they said.
If the data can be translated into human studies, the implications could be highly significant. There are an estimated 28 million people in the United States alone with type-2 diabetes. There are also numerous diseases associated with liver fibrosis, including cirrhosis, which is one of the leading causes of death across the globe, Yale said.
