Dec. 7, 2000 -- Thanks to Canadian researchers and gene therapy, diabetics may one day be free from the hassle of daily insulin shots and some of the complications that go along with their disease.
A team of scientists at the University of Alberta in Edmonton injected fertilized mouse eggs with a gene that caused special cells, called K cells, in the animals' stomach and upper intestine to release insulin into the bloodstream -- a job normally performed by the pancreas.
The type of diabetes the treatment is designed for -- type 1 or juvenile diabetes -- results when the pancreas fails to produce insulin. Insulin is a hormone that "unlocks" cells, allowing sugar to enter and produce energy to fuel the body. Since sugar can't enter the cells, it builds up in the blood and the body's cells literally starve to death. There are an estimated 500,000 to 1 million people with type 1 diabetes in the U.S., according to the American Diabetes Association.
People with type 1 diabetes must frequently monitor their blood sugar levels and take insulin injections to stay alive. Diabetes can lead to many problems, including heart and kidney disease, blindness, and limb amputation.
In the study, scientists were able to trigger these K cells to produce insulin in a way that mirrors how it's done in a nondiabetic -- after meals and in proportion to the amount of sugar consumed in that meal. The timing of insulin release is critical in controlling the body's blood sugar -- or glucose -- levels and mimicking this natural process has been a long sought after goal of scientists.
That's why Tim Kieffer, PhD, lead researcher on the project, says that genetically altered K cells are a particularly promising target for a new diabetes treatment. "We've genetically engineered these cells in the gut to produce insulin in a meal-regulated fashion. Sugar levels go up promptly after meals" with the amount dependent on the amount of sugar taken in, says Kieffer.
While other researchers have successfully used gene therapy to make other tissue or organs in the body -- such as the liver or pituitary gland -- release insulin, they have not been able to trigger that release right after meals.
David Lau, MD, PhD says Kieffer's approach is innovative because of this instantaneous release by K cells of insulin in response to meals. "There is not the time lag -- which can be up to a few hours -- between ingestion of glucose [in a meal] and corresponding release of insulin." Delay of insulin release can result in serious complications such as hypoglycemic shock where the blood sugar drops to dangerously low levels causing tremors, confusion, coma, and even death.
Another beauty of this approach, says Kieffer's co-researcher, Anthony Cheung, PhD, is that they've put to work cells that are already wired to respond to food intake. "We haven't reinvented the wheel here. Rather, we're inducing existing glucose-responsive cells to produce insulin," which takes advantage of their natural ability, he says.
Kieffer is the first to point out that people won't be able to benefit from his research for a long, long time. "It will be many more years until we might have this working in animals, and more years after that before it could be tested in humans," says Kieffer. The team's next step, he says, is to find a means of successfully introducing the gene into the intestine of an adult mouse.