Scientists find protein that helps insulin cell growth

by Barbara Hewitt on December 25, 2015

Scientists in the United States have identified a key protein produced in the liver that helps increase the growth of the body’s own insulin producing pancreatic beta cells.

If the research progresses well it could help to boost beta cell growth with significant implications for the treatment of both type 1 and type 2 diabetes.

Scientists Lab“Making more functional beta cells is critical for treating all forms of diabetes,” said Rohit Kulkarni, a senior investigator for islet cell and regenerative biology at the Joslin Diabetes Centre in Boston and professor of medicine at Harvard Medical School.

If his team is successful in using proteins that normally circulate in human blood as growth factors for beta cells, the approach may progress toward clinical trials more quickly than some potential therapeutic alternatives.

“This is because it takes away the uncertainty of what a foreign compound or a foreign molecule does to other tissues in the body,” Kulkarni said.

The team found that a protein called serpinB1 can significantly boost beta cell growth in humans, mice and zebrafish. Mice that were genetically engineered to lack the protein also displayed diminished ability to grow beta cells.

Additionally, the researchers demonstrated that levels of serpinB1 in human blood are higher in people with insulin resistance, a condition that is a precursor to developing diabetes. People with this condition may prevent developing diabetes by compensating and generating more beta cells, which are located in the clusters of pancreatic cells known as islets, due to the growth effects of serpinB1.

The researchers began their work in mice genetically modified to create insulin resistance in the liver. In an earlier study with this mouse model, which heightens the production of beta cells, they had discovered that proteins released from the liver and circulating in the blood were driving the increased proliferation of beta cells.

In the current study, the Joslin scientists analysed the proteins present in blood plasma from these mice and in the fluid surrounding their liver cells in culture. In both analyses, the researchers saw strikingly high levels of serpinB1. The serpinB1 gene was also highly expressed in liver cells.

The scientists knew that one of serpinB1’s roles is to inhibit activity of elastase, an enzyme that cuts one component of connective tissue. They identified two commercial elastase inhibitors and found that both compounds raised boosted beta cell production in mouse islets. One of the compounds also did so in human islets.

Next, the researchers transplanted human islets into a mouse with a depleted immune system, along with a tiny pump that released the elastase inhibitor for two weeks. The human beta cells proliferated, as did the mouse’s own beta cells.

Even more dramatically, when these fish were given a compound that destroyed all their beta cells, the researchers could see new beta cells appearing.

“This may have particular implications for treating type 1 diabetes, in which most of the beta cells are gone,” Kulkarni explained.

Kulkarni and the team are now looking more broadly across various populations of people with diabetes both for serpinB1 mutations and for the levels of the protein in the blood and examining how the protein is regulated and the molecular mechanisms by which it boosts beta cell proliferation.

“Overall, identifying growth factors that naturally circulate in the blood offer potentially major advantages for building healthy beta cells and we look forward to moving ahead rapidly with work to translate this research toward clinical use,” said Kulkarni.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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