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Liver protein enhances growth rate of insulin-producing cells, study finds

Researchers at the Joslin Diabetes Centre have identified a key liver protein that boosts the growth of insulin-producing beta cells.
The protein, call serpinB1, boosted beta cell growth in humans, mice and zebrafish. When the researchers engineered mice to lack serpinB1, those mice were less able to grow beta cells.
This is a preliminary study, and more research is needed, but the findings could lead to more effective treatments for people with either type of diabetes.
“Making more functional beta cells is critical for treating all forms of diabetes,” said Rohit N. Kulkarni, Senior Investigator in Joslin’s Section on Islet Cell and Regenerative Biology at Joslin Diabetes Centre and Professor of Medicine at Harvard Medical School.
In a previous study, the researchers noticed that mice that were genetically engineered to have insulin resistance in the liver had much higher levels of serpinB1 in the blood. They observed that liver proteins – including serpinB1 – were causing an exponential growth of beta cells.
The researchers worked with Eileen Remold-O’Donnell, of Boston Children’s Hospital, whose research team built a synthetic version of serpinB1. They used this version to incubate islet cells from both humans and mice. In both cases, beta cells grew significantly.
To widen their understanding of serpinB1, the researchers engineered a zebrafish model with excessively high levels of serpinB1. Again, they observed a proliferation of beta cells. When the researchers destroyed their beta cells, the high levels of serpinB1 restored new beta cells. “This may have particular implications for treating type 1 diabetes, in which most of the beta cells are gone,” said Kulkarni.
When the researchers grew beta cells using synthetic serpinB1, those beta cells secreted insulin in a normal, functioning way. Because the beta cells appear to work naturally, there are fewer questions surrounding this method about long-term stability. When beta cells are created using stem cells, for example, sustainability is a pressing issue. Using proteins found naturally in the blood to grow beta cells has distinct advantages, says Kulkarni, “and we look forward to moving ahead rapidly with work to translate this research toward clinical use.”
If the next stages of research are successful, it won’t take too long to conduct clinical trials based on the findings, “because it takes away the uncertainty of what a foreign compound or a foreign molecule does to other tissues in the body.”
The findings are published in Cell Metabolism.

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