The insulin shortage in diabetes

A healthy pancreas contains about a billion beta cells that produce insulin. In people with diabetes, these cells are missing or broken, so scientists are searching for ways to replace them.

Ductal cells hint at a solution

Researchers at Harvard Medical School discovered that pancreatic ductal cells occasionally transform into beta cells on their own, an unusual ability in adult cells. This suggested they could be engineered to do it more reliably.

Finding the genetic switch

Jian Li, a postdoctoral researcher at Harvard Medical School, led a study using a genetic screen to identify which genes drive the transformation. The team systematically disabled genes across the genome to find the key ones.

Silencing ALDH3B2 boosts transformation

When researchers silenced the ALDH3B2 gene, ductal cells transformed into beta-like cells at about eight point five percent, compared to fewer than one percent without the alteration. The effect was published in Science Translational Medicine.

Proof in mice with diabetes

The team transplanted altered human cells into mice with diabetes. Human insulin circulated in the animals and their glucose levels dropped to near-normal levels, an effect that persisted for six weeks.

Next steps and remaining challenges

Jian Li said the team must first verify how ALDH3B2 drives the transformation, then test gene therapy or small molecules to inhibit it. Precision is critical because ALDH3B2 is used by many cells throughout the body.

“That's the part we need to verify first. Then, the next step is either gene therapy or to find specific small molecules to inhibit this gene to see if we can achieve a similar, or even better, effect.”