With over 37 million Americans with diabetes, it is, without a doubt, a major public health concern. Today, it is common to either have diabetes or know someone with it due to its increasing prevalence. And naturally, this bears a considerable cost. In 2021, the healthcare cost of diabetes in the United States was $237 billion. In addition, $90 billion can be attributed to the lost productivity brought on by diabetes. Therefore, so much more is needed, and it’s possible that plants might be just the thing to save the day.

Keep reading to learn more about the evolution of insulin and how groundbreaking plant revelations may be able to remedy many of the issues brought on by traditional insulin treatment.

The Link Between Insulin and Diabetes

According to one cross-sectional study, 52% of participants with diabetes had inadequate knowledge of insulin therapy. Therefore, it’s only right that we shed light on what it is and its role.

Insulin is a hormone that plays a critical role in converting food into energy while also maintaining blood glucose levels in an ideal range. In individuals without diabetes, the pancreas produces the right amount of insulin to meet these needs. However, for patients with diabetes — both Type I and Type II — there is an insulin failure.

With type 1 diabetes, insulin-producing cells in the pancreas are targeted by an autoimmune reaction. This results in the body not having enough insulin to maintain consistent blood glucose levels. As a result, most adults with this condition require multiple daily insulin injections to supplement the lack of insulin their body produces.

On the other hand, with type 2 diabetes, the human body, over time, builds up insulin resistance. As a result, it eventually requires more and more of it to be produced to manage glucose levels. Generally, a lack of insulin will lead to high blood sugar levels (hyperglycemia) since glucose will not reach the cells that need it for energy. Occasionally, insulin replacement therapy is combined with oral glycemic medications to maintain glycemic control.

A Brief History of Insulin

The existence of diabetes as a potentially deadly disease has been known for more than two millennia and was discussed in ancient Egyptian texts. However, before discovering what caused diabetes and how to potentially approach treating it, most patients had an extremely short lifespan following diagnosis. The only way to control the disease was through extremely restrictive diets, and many patients noted that the ‘cure’ was worse than the disease. The ‘cure’ was often a starvation-level diet with no carbohydrates, and many patients died from malnutrition.

More than a century ago, scientists made the breakthrough revelation that diabetes was caused by problems with the pancreas. After additional experimentation, including removing the pancreas from laboratory dogs, they discovered that it was more specifically a failure of the pancreas to produce insulin. However, this breakthrough did not immediately solve the problem of how to reintroduce insulin into the body of people dealing with diabetes.

Animal-Based Insulin

Initially, researchers discovered that they could take insulin from other animals and inject it directly into the diabetic patient. Early experiments used insulin extracted from dogs’ pancreas and showed significant positive effects in the patients receiving the animal-based insulin.

Interestingly, the first patient to receive this animal-derived insulin survived for more than ten years, which was almost unheard of at that time for patients with diabetes. Prior to that, lifespan was often counted in weeks or months.

The scientists who initiated this experiment received the Nobel Prize in Medicine, but the solution was still far from perfect. Over time, the insulin that was used came primarily from cows and pigs. However, some individuals had allergic reactions to this foreign body. In addition, there was an almost constant struggle to ensure that supply kept up with the growing demand for insulin. This was partly driven by the fact that it took approximately two tons of pig waste product to extract eight ounces of usable insulin that had been purified to make it human-grade.

Researchers continued to experiment with ways to make insulin more effective. For instance, zinc was added to insulin to extend its action time. Protamine was another addition to insulin, prolonging its action period to more than twenty-four hours. This was a significant added benefit for many patients, compared with traditional short-acting insulin that could lead to dramatic spikes and dips in glucose levels.

The Development of Synthetic Insulin

It was not until 1978 that researchers came up with a more effective solution in the form of synthetic insulin derived from E. coli bacteria. This early synthetic version of the drug continues to be refined using rDNA techniques. The advent of synthetic insulin helped guarantee that supply would keep up with a continued uptick in demand as more people are diagnosed with diabetes.

Even though synthetic production methods increased the available supply and eliminated the allergenic challenges of animal-based insulin (since it is bio-identical to human insulin), a barrier still stands before us.

Prices remain high, and many people struggle to afford their life-saving insulin. In fact, for decades, animal-derived insulin remained significantly cheaper than the synthetic options that were being produced.

This price struggle has nudged scientists to look for alternative production methods for insulin, such as plant-based insulin.

Wait, Did Someone Say Plant-Based Insulin?

For years, the medical community has known that some plants hold the secret to potentially curing rare and challenging diseases, including many types of treatment-refractory cancer. However, when we think about these plants, we tend to think about unusual species lurking in the depths of the Amazon rainforest. We tend not to think about common vegetables.

However, it turns out that a simple head of lettuce may hold the secret to developing plant-based insulin.

What Exactly Is Plant-Based Insulin?

As mentioned before, insulin is a hormone naturally produced in the human pancreas, but it can also be developed in a laboratory using recombinant DNA technology. However, as you might imagine, this process can be costly and time-consuming, which has led some scientists to look for alternatives.

One of these potential alternatives is plant-based insulin.

In this process, genes associated with human insulin are extracted from human cells and reintroduced into the plant’s cells. In this case, lettuce. Seeds from these lettuce plants all maintained human insulin genes into future generations. Once these lettuce seeds develop into lettuce heads, they can be harvested and processed for their insulin. In fact, future generations seemed to produce more insulin than the original plant, although this still requires more scientific exploration.

Scientists hypothesize that this approach will be more cost-effective. The plant-based insulin is also shelf-stable, meaning it can be shipped and stored in remote regions without significant concerns. Currently, traditional insulin is slightly more challenging to deliver due to its need to be refrigerated.

What a Study Revealed about Lettuce and Insulin

Traditional insulin production in the laboratory utilizes bacteria or yeast as the medium to multiply insulin in a costly and time-consuming process. This study, however, illustrates that genetically modified lettuce cells can be an adequate substitute for bacteria or yeast.

The most challenging part of this process was inserting insulin genes through the plant’s rigid cell walls. Conquering this problem required scientists to develop a so-called gene gun. However, these strong cell walls were also protective and stopped the insulin from degrading in the stomach before reaching the liver and bloodstream. This result differed from previous plant-based trials that struggled with stomach acid breakdown.

Once the insulin was developed, scientists tested its efficacy on diabetic mice. They found that the plant-based insulin had a more controlled decrease in blood glucose than traditional insulin and avoided problematic rebound hypoglycemia.

Perhaps the most significant benefit of this plant-based insulin is that a patient would take it orally. The genetically modified lettuce is freeze-dried and ground up before being delivered to the patient. This allows patients to avoid the pain and discomfort associated with injectable insulin.

A Potentially Better Treatment On The Horizon

Diabetes management is not only burdensome on an individual level but also to society as a whole. As traditional insulin treatment presents many barriers, researchers have felt compelled to find innovative and cost-effective solutions, like the potential use of plant-based insulin.