Lettuce and Diabetes

Can insulin produced in lettuce cure type 1 diabetes some day? Possibly. In mice, it seems to modulate the immune attack on the beta cells that is the hallmark of type 1 diabetes. But the pathway is complex.

Therapeutic insulin is usually injected. This is for two reasons. First, most proteins are partically digested in the stomach. The very acid stomach first denatures the proteins. This means that the very specific folding of a protein that gives it specificity is destroyed, and the protein goes from a compact structure to a long chain of amino acids (the building blocks of proteins).

Then the digestive enzyme pepsin, which works best in an acid environment like the stomach, begins to chop the long chain into smaller bits. Hence, no more insulin.

The second reason is that in a healthy person, the gut easily absorbs small molecules like glucose or individual amino acids. It doesn't usually absorb a lot of proteins in their intact form. So even if insulin were able to make it through the stomach, it wouldn't be absorbed very well.

Inhaled insulin was developed as one way to get around these two problems. There's no acid in the lungs, and they are able to absorb some of the inhaled insulin intact. Insulin sprays in which the insulin is absorbed through the skin of the mouth are another approach.

Now researchers at the University of Central Florida, led by Henry Daniell, are working at an ingenious method to allow insulin -- as well as various vaccines -- to be delivered orally to the gut, where the insulin can act as an immunomodulator, a substance that modulates your immune system response.

First, they're producing the proteins in genetically modified plants. They've used tobacco and, more recently, lettuce to produce human proinsulin (the compound that is broken down in the beta cells into insulin and C-peptide).

Other researchers have produced insulin in other plants, for example, safflower. But by inserting the insulin gene in the plant chloroplasts -- the tiny organs in plant cells that take energy from the sun and use it to make carbohydrates -- Daniell's group has gotten high yields of proinsulin without the danger that the altered genes will spread through pollen. This is because chloroplasts are inherited only through maternal cells, not through pollen (male cells).

Next, by grinding up the plant tissue and feeding the ground up tissue to mice, they've managed to bypass the protein destruction that usually occurs in the stomach. In essence, the plant cells with their cellulose walls are encapsulating the proinsulin and protecting it. Once in the intestine, the plant cells are slowly digested and the proinsulin complex is released.

That leaves the last problem: the fact that intestinal cells don't take up intact proteins very well. To solve this problem, they've complexed the proinsulin with something called cholera toxin B. This is a nontoxic part (the B subunit) of cholera toxin that stimulates intestinal cells to take up proteins.