Researchers Discover Body’s Own Proteins Could Regrow Beta Cells

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A new study from Dr. Kulkanri shows a protein in the liver increases the rate of beta cell growth

A key to curing diabetes in all of its forms is figuring out a way to regrow beta cells. Ideally, this would be done using something that the human body already produces to avoid the long delays and other drawbacks of introducing a new drug.

Researchers at Joslin have made some headway in that department, recently announcing their discovery that a protein produced in the liver increases the rate of beta cell growth. The protein, called serpinB1, was studied in humans, mice and zebrafish. In all three organisms the protein showed a positive correlation to beta cell growth. And in one striking experiment, beta cells that had been completely wiped out began to grow again.

SerpinB1 already shows up in high levels in the bloodstreams of people with insulin resistance who have not yet developed type 2 diabetes. This makes sense, because as people develop stronger and stronger insulin resistance, their bodies have to work harder to keep up with the insulin demand by creating new beta cells to delay onset of overt diabetes.

Joslin’s Rohit Kulkarni, M.D., Ph.D., Senior Investigator in the Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School, led the team of researchers that tested serpinB1 in multiple circumstances to check and double check that their hypothesis was correct. This study was inspired by a previous observation that mice genetically modified to have insulin resistance seemed to have liver-released proteins stimulating the growth of their beta cells.

Dr. Kulkarni and his colleagues started this round of experiments by pinpointing which liver-related protein was responsible. They saw high levels of serpinB1 circulating in the blood stream. They also noticed that the gene in charge of telling liver cells to release serpinB1 was switched on more frequently in the insulin resistance mice than would be expected in a healthy mouse.

They took these findings to collaborators at Children’s Hospital Boston, who had previously developed a synthetic version of the protein. They put this synthetic serpinB1 in culture dishes with either mouse or human islets. In both cases, they saw the beta cell mass increase.

They were confident that the protein stimulated the growth of beta cells, but they wanted to test why. So they found two different medications that perform the same role as the naturally occurring serpinB1 (which is stopping the activity of a certain enzyme) and repeated the culture dish experiment. The results were the same.

Now that they had determined what happened when serpinB1 was in the body, they wanted to see what would happen if it was taken away. They put mice which were modified to not produce serpinB1 and healthy mice in situations that should increase beta cells; in one experiment they were fed a high-fat diet, and in another they were given a compound meant to raise blood glucose. In both experiments, the mice without serpinB1 regenerated fewer beta cells than the healthy mice.

They further tested their hypothesis in a completely different organism—the zebrafish—with the same results. Of note, when the researchers erased all of the zebrafish’s existing beta cells, they saw new beta cells appearing under the influence of extra serpinB1.

Since publishing these findings, Dr. Kulkarni and his colleagues have continued to investigate the relationship between serpinB1 and beta cell growth by studying more people with both type 1 and type 2 diabetes to understand exactly how the protein works and also whether it can serve as a biomarker.

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One Response to Researchers Discover Body’s Own Proteins Could Regrow Beta Cells

  1. 1m88 says:

    Congratulations both on the scientists who made this discoveries and patients who are in diabetes conditions. Hope the finding will bring new therapies for diabetes.

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