Repurposed cancer drug could treat diabetes by nudging pancreatic acinar cells to produce insulin
Key Takeaways
- Researchers have demonstrated that a drug previously studied for cancer treatment can convert acinar cells into insulin-producing cells and regulate blood sugar in diabetic mice and non-human primates.
- The findings suggest that the drug could serve as a novel treatment for diabetic patients.
In 2016, University of Pittsburgh researchers Dr. Farzad Esni, Ph.D., and Jing Hu, Ph.D., did an experiment in mice where they deleted one of two copies of the gene encoding an enzyme called focal adhesion kinase (FAK). They were interested in the role of FAK in pancreatic cancer, but a surprising finding took the research in a very different direction. “The pancreas looked weird, almost like it was trying to regenerate after an injury,” said Esni.
Even weirder, a cluster of cells in the pancreas was expressing both insulin and amylase. In normal mice and humans, the blood sugar-regulating hormone insulin is produced by beta cells, while amylase, a digestive enzyme, is manufactured by acinar cells. The functions of acinar and beta-cells are very distinct, so it didn’t make sense that the cluster of cells looked like a combination of the two. “There were three possible explanations for what we saw in the mutant mice,” said Esni. “It could have just been an artifact of our experiment, beta cells could have started making amylase or acinar cells could have started producing insulin—which would be the holy grail.”
Esni and his team had in fact stumbled upon this holy grail. In a new Nature Communications paper, the researchers show that a FAK-inhibiting drug, which has been studied in cancer treatment, converted acinar cells into acinar-derived insulin-producing (ADIP) cells and helped regulate blood glucose in diabetic mice and a single non-human primate. The findings suggest that FAK inhibitors could be a new avenue for treatment and potentially replace insulin therapy in diabetic patients.
The idea of nudging acinar cells to produce insulin isn’t new, but FAK inhibitors may have a smoother translational path than genetic approaches because the drug has already been tested in phase 1 cancer trials. It’s also given orally, which is simpler than complicated genetic tools that involve viral delivery of foreign genes or genetic factors that switch on genes.
With the eventual hope of launching a clinical trial to test FAK inhibitor in diabetes patients, Esni and his team are now planning long-term experiments in mice to look at the duration of hyperglycemia (high blood sugar) control after a single course of the drug in mouse models for type 1 or type 2 diabetes. They’re also investigating the effects of FAK inhibition in pancreatic tissues from human donors.
Edited by Miriam Kaplan, PhD
Source: University of Pittsburgh, Medical Xpress, May 6, 2024; see source article