While clinical insulin is lifesaving for the estimated 537 million adults living with diabetes worldwide, it comes with some risks to patients. Recent studies show that injection via insulin pens can cause insulin to reach the bloodstream so quickly that hypoglycemia, or blood sugar levels that dip below the healthy range, may result. Automated insulin pumps can minimize this risk, but are expensive and available only to a small portion of diabetes patients worldwide.

Now, a plant-based, oral delivery of proinsulin could address these drawbacks, according to a study published in Biomaterials, led by Henry Daniell of Penn Dental Medicine.

Although clinical insulin has been in use for decades, it is missing one of the three peptides that occur in natural insulin. The Daniell lab created a plant-based insulin that contains all three peptides and can be ingested orally. The strength of plant cell walls protects insulin from acids and enzymes in a patient's stomach before the material is broken down by gut microbes. Then, the released insulin is delivered to the liver via the gut-liver axis.

Using diabetic mice, Daniell and his team found that their plant-based insulin regulated blood sugar within 15 minutes of ingestion -- very similar to naturally secreted insulin. In comparison, mice treated with traditional insulin injections experienced rapidly decreased blood glucose levels leading to transient hypoglycemia.

To produce plant-based insulin, scientists identified human insulin genes and then used what Daniell calls a "gene gun" to blast the genes through the plant cell walls. The insulin genes are then integrated into the plant's genome, in this case the lettuce genome. The resulting seeds permanently retained insulin genes, and subsequently grown lettuce was freeze dried, ground, and prepared for oral delivery following FDA regulatory guidelines.

This process is vastly different from producing insulin in the traditional manner, which involves growing the hormone in bacteria or yeast cells, an expensive process requiring purification and a low temperature for transportation and storage. Daniell's production method eliminates the need for expensive, complex laboratory equipment and the resulting product is shelf stable at room temperature.

Going forward, Daniell plans to test plant-based insulin in canine and human subjects.

"Affordability and global access to health care are the foundation for my work," Daniell says. "In this case, we are making insulin more affordable, while significantly improving it."