(PALO ALTO) – For 20.8 million Americans suffering from diabetes, hope might lie in the recent findings by a team of Stanford scientists.

Some might call it a breakthrough, a gateway to new remedies and possibly cures for diabetes patients. Dr. Jeremy Heit, an MD/Ph.D. student, calls it his thesis.

“It is a culmination of four years of work,” Heit said of the findings, which were published in the Sept. 21 issue of Nature magazine. “The results are exciting.”

Working with Dr. Seung Kim, assistant professor of developmental biology and medicine at the Stanford Medical School, Heit uncovered some of the intricate biochemical links between calcineurin, NFAT and insulin.

The four-year-long journey, appropriately, began and ended with patients.

It started with a question at Kim’s lab: Why do 30 percent of organ transplant patients who use certain kinds of immunosuppressant drugs get diabetes?

To understand this, one must first get familiar with the disease, Heit said.

According to the American Diabetes Association, diabetes is the sixth leading cause of death in the United States. It occurs when the body does not produce enough insulin or does not use it correctly. Insulin helps muscles, fat and the liver take in sugar and store it as energy — at the same time lowering the amount of sugar in blood so the excess doesn’t damage blood vessels, kidneys and other tissues.

“When you eat a meal, the sugar level in your bloodstream rises,” Heit explained.

Beta cells in the pancreas then sense the rise and respond by producing and releasing insulin to the bloodstream, he said. A shortage of insulin or a failure of the hormone to function properly results in diabetes.

From these facts, Heit and his team reasoned that since organ transplant patients get diabetes so often, the immunosuppressant drugs they are using must target something that affects beta cells.

They were right.

That “something” was calcineurin, a protein the drugs are known to suppress. Heit found that the absence of calcineurin led to diabetes.

Heit and Kim made this discovery with the help of Dr. Gerald Crabtree, Stanford professor of developmental biology and pathology, who lent his biochemical expertise — and lab mice — to the project.

Heit and his team “deleted” the calcineurin from the beta cells of a group of mice.

As they predicted, the mice developed severe cases of diabetes within weeks.

In further investigations, Heit found that calcineurin played a central role in beta cell growth and its production and release of insulin.

The findings don’t stop there.

Heit’s team has also discovered a new way for future drugs to stimulate insulin production and function in type II diabetics: The protein NFAT.

One of his experiments showed that because of the missing calcineurin in the mice, six genes known to be responsible for beta cell growth and insulation production were not “turned on,” according to Heit.

What’s more, these same genes and several others are directly controlled by another type of protein called NFAT.

The next logical step was to “turn on” NFAT in the mice and see what it did. The team of scientists found this action gave them the opposite results of deleting calcineurin; it stimulated beta cell growth and produced and released more insulin.

“[These results] hint that a new class of drugs that activate NFAT proteins [or calcineurin] might be useful as a therapy for type 2 diabetes could trigger an entirely new arena of further diabetes research.”

In the future, new drug and stem cell therapies derived from these results could also be engineered.

“The process of taking this new discovery to the point of new treatments or potential cures will take many years,” said Dr. John Buse, president-elect of the American Diabetes Association, “but it is clearly an opportunity in play now.”