Envisioning a cure for diabetes

Contra Costa Times // Tue, July 12, 2005

By Betsy Mason

Diabetes is one of the most promising targets of stem cell research. People with this disease have problems with insulin, a hormone in the pancreas that regulates blood sugar levels. Patients have poorly functioning or too few insulin-producing cells, known as beta cells.

"We think that ultimately the way to cure people with diabetes, or at least many patients with diabetes, is to replace those cells," said Michael German of the UC San Francisco Diabetes Center.

Several clinics worldwide, including UCSF, already do this by transplanting beta cells from cadavers into diabetes patients.

"The problem is, at present we don't have nearly enough cells to do this," German said.
There are more than 150 million people with diabetes and more than a half million new cases each year in the United States alone. But fewer than 5,000 pancreases are available for donation yearly, he said.

"If we had an unlimited supply of these cells, we could treat everybody with diabetes," German said.

He hopes stem cells can help generate that supply.

In normal human development, some stem cells eventually become beta cells. The cells face a series of decisions that lead them down the path to becoming insulin-producing cells or another cell type. To become a beta cell, they must first decide to become part of the gastrointestinal tract, and eventually part of the pancreas, and then part of the pancreas area that contains specialized cells, including beta cells. Finally they must decide to become a beta cell.

German is working on how to coax embryonic stem cells along this path.

"The programs by which those decisions are controlled at a molecular level is what my laboratory has been focused on," he said. "The idea is that if we knew the genes and the signaling pathways that control each of these decisions that we could in fact take embryonic stem cells and drive them specifically to make these decisions and end up as beta cells."

He and other scientists have already identified some genes along the pathway in mice, and there is good evidence that the same pathway exists in humans.