New Source of Insulin Discovered

Insulin is like gold to a diabetic, and researchers at Harvard Medical School have found a new way to mine it.

The hormone is essential for converting sugar in food into energy; without regular injections of it, people suffering from Type 1, or juvenile, diabetes can lapse into a coma and die. Medical scientists have proposed treating this type of diabetes by transplanting islet cells, which produce insulin, from the cadavers of nondiabetics. Recently, Canadian specialists announced that they have done this successfully in eight consecutive patients. These diabetics have gone for as long as 15 months without insulin shots.

But even if such transplants work, there still will not be enough islet “gold” to go around. About 800,000 people in the United States have the disease, and about 30,000 new cases occur every year, while only 3,000 suitable cadavers become available each year. In addition, it takes two cadavers to obtain enough insulin cells for one transplant.

With that problem in mind, researchers at Harvard-affiliated Joslin Diabetes Center in Boston have coaxed cells that normally do not produce insulin into doing so. In fact, these cells are thrown away when islet cells are removed from donor bodies.

“We were able to take lead and make gold from it,” said Susan Bonner-Weir, an associate professor of medicine. “This is the first time this has been done and it has exciting promise.”

Islet cells are located in the pancreas, a gland that lies across the back of the abdomen behind the stomach. A network of ducts carries insulin and proteins made for digestion from the pancreas to the small intestine.

When they first form in the embryo, duct cells can develop into islet cells or cells that secrete digestive juices. But when they mature, these cells lose most of their capacity to secrete insulin and settle down as part of the plumbing.

Bonner-Weir and her colleagues developed an alchemic process that turns back the clock for duct cells, coaxing them into producing islets that secrete useful amounts of insulin. Nurtured in laboratory flasks for three or four weeks, the cells increase their insulin production 10 to 15-fold.

That’s exciting, but it’s still short of solving the problem. Bonner-Weir estimates that her experiments produced only 32,000 islet cells, not nearly enough for a successful transplant. “However, she says, “I’m optimistic that we can modify our technique to get significantly more insulin-producing cells.”

Her optimism comes from work already done with the duct cells of rats and pigs. And she is in contact with several other labs that are working on the same problem.

“I think we can reach this goal in the next couple of years,” Bonner-Weir says.

The Joslin Diabetes Center is confident enough to say that if enough insulin can be produced this way, it might be used for Type 2, or adult-onset, diabetics, patients who outnumber Type 1s more than 15-to-1. Type 2 diabetics have cells that produce insulin, but they either don’t produce enough or the person cannot use that insulin to keep blood sugars under control.

Bonner-Weir is cautious about such use. Transplantees have to take drugs to prevent rejection of the new insulin cells, just as the recipients of heart and liver transplants do. That’s not a bad trade-off for those whose lives are threatened by Type 1 diabetes, and an endless routine of insulin injections and dieting. But diabetics who can control their sugar levels by dieting might not want to trade that off for a lifetime of taking anti-rejection drugs and dealing with possible side effects.Bonner-Weir and her colleagues describe their research in the July 4 issue of the Proceedings of the National Academy of Sciences.