Insulin production has, for the last 50 or so years, come with some risks to the patient. Even so, the medication is necessary for the estimated 537 million adults with diabetes worldwide, with that number expected to grow. Recent clinical studies show that injection via insulin pens can cause insulin to reach the bloodstream so quickly that blood sugar levels drop below the healthy range. Automated insulin pumps can deliver precise insulin and minimize this risk but are expensive andavailable only to a small portion of diabetes patients around the world. Now, a plant-based, oral delivery of proinsulin could address these drawbacks, according to a new study led by Dr. Henry Daniell of Penn’s School of Dental Medicine. Although clinical insulin has been in use for several 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 similarly to naturally secreted insulin. In comparison, mice treated with traditional insulin injections (es. Actrapid and Humulin S are the most commonly used) experienced rapidly decreased blood glucose levels, leading to transient hypoglycemia. In people this may transalte in fainting. Daniell has long researched uses for plant-grown proteins. In a study published in 2015, he or the first time, demonstrated the commercial viability of producing a low-cost drug made from lettuce plants. In that paper, researchers used freeze-dried lettuce leaves to produce an effective drug for hemophilia patients.
Daniell has also worked on plant-based medicines to treat pulmonary arterial hypertension, Alzheimer’s disease, muscle traumas (with the insulin cousin IGF-1), polio and created a plant-based gum that reduces the viral load of COVID-19 in saliva. 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 tough 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 results in a product that is shelf stable at room temperature. He thoroughly explained: “We’ve seen news stories about vaccine doses being destroyed because some countries don’t have the resources for cold storage throughout the process. It is an enormous cost. This kind of post-production cost is eliminated using our methods because we have shown repeatedly that the product is shelf-stable. For people, plant-based delivery of medicines could dramatically alter treatment for diabetes and other diseases. With this delivery system, we change the whole paradigm, not only for insulin. I grew up in a developing country and saw people die because they couldn’t afford drugs or vaccines. For me, affordability and global access to health care are the foundation for my work. And in this case we are making insulin more affordable while significantly improving it: patients can get a superior drug at a lower cost”.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Daniell H, Singh R et al. Biomaterials. 2023 Jul; 298:122142.
Park J et al., Daniell H. Biomaterials. 2020 Mar; 233:119591.
Posgai AL, Wasserfall CH et al. Sci Rep. 2017 Feb; 7:42372.