University of Pittsburgh

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Breakthroughs in the Making

How To Make An Insulin Factory

Written by Laura Powers

Millions of Americans live with diabetes. The disease is linked to insufficient insulin, which is needed to fuel cellular energy. Insulin, a hormone, enables glucose to enter cells and produce energy. In people with diabetes, this process isn’t working. Diabetes debilitates the body and increases the risk for heart attack and stroke. Over time, many diabetics suffer from eye problems and kidney disease, and others lose limbs from nerve damage.

Imagine if these problems could all go away.

University of Pittsburgh researchers have made a discovery that moves scientists closer to that goal. The team—led by Andrew F. Stewart, a professor of medicine, and Nathalie Fiaschi-Taesch, an assistant professor of medicine—has been able to induce replication of human insulin-producing cells, known as beta cells.

The Pitt group discovered that insulin-producing human beta cells contain considerable amounts of the protein cdk-6, which modifies the function of other proteins and molecules. The team found that it could replicate and multiply beta cells by boosting production of the protein through manipulation of the cdk-6 gene. Further, the team was able to stimulate creation of additional human beta cells by boosting production of cyclin D1, a molecule that’s vital in a cell’s cycle of life.

When the team’s engineered human beta cells were transplanted into the kidney of a diabetic mouse, the cells continued to replicate, and blood sugar levels stabilized and normalized. When the engineered cells were removed, the mouse again developed diabetes.

These findings give new hope to all who are afflicted with diabetes. “This work provides proof-of-principle that the production of human beta cells can be stimulated and that the newly generated cells function effectively both in the lab and in a living animal,” says Stewart, who also is chief of the Division of Endocrinology and Metabolism in Pitt’s School of Medicine.