Imagine a pill that helps people control diabetes with the body’s own insulin to lower blood glucose levels. Cornell researchers have achieved this feat in rats by engineering human lactobacilli, a common gut bacteria, to secrete a protein that modifies intestinal cells to produce insulin.
A 2003 study led by Atsushi Suzuki of the University of Tsukuba, Japan, first demonstrated that when exposed to a protein called Glucagon-like peptide 1 (GLP-1), intestinal epithelial cells (which cover the guts) are converted into insulin-producing cells.
But until now, it has not been possible to administer GLP-1 into a live animal without injecting it, a method of administration that is not very effective.
The researchers came up a clever way to secrete GLP-1 in the gut without injecting it:
1. They engineered a strain of lactobacillus, a human probiotic (“good bacteria”), to secrete GLP-1.
2. They administered the modified probiotic bacteria orally to diabetic rats for 90 days.
3. Upper intestinal epithelial cells in diabetic rats were converted into cells that acted very much like pancreatic cells (cells that monitor blood glucose levels and secrete insulin as needed to balance glucose levels in healthy individuals).
4. Rats with high blood glucose (called hyperglycemia, a hallmark of diabetes) that received the engineered probiotic ended up with up to 30 percent lower blood glucose levels.
A pill instead of an injection
The rat study was a proof of principle; future work will test higher doses to see if a complete treatment can be achieved, said John March, professor of biological and environmental engineering in the College of Agriculture and Life Sciences and the paper’s senior author.