MEDICINE / DIABETES : Animal Insulin Tests Raise Hope for Artificial Pancreas

Animal researchers reported Sunday a major advance toward the development of an artificial pancreas that could provide long-lasting therapy for diabetes--without daily insulin injections--and potentially eliminate its crippling side effects.

The Massachusetts scientists devised a technique that allows them to transplant insulin-secreting pancreatic cells from cows, dogs and pigs into rats without suppressing the recipient’s immune system and without fear of rejection. The transplanted cells, encased in newly synthesized, porous, hollow fibers, release insulin that controls blood sugar levels precisely.

Scientists have been trying to use human pancreatic tissues to treat some of the more than 1 million insulin-dependent diabetics in the United States, but the number of human pancreases that can be obtained from cadavers is quite small. If researchers could develop a successful technique for using pancreatic tissue from cows, for example, the number of people that could be treated potentially would be limitless.

Researchers have been attempting to construct such artificial pancreases for more than two decades, but the new advance, reported Sunday in the prestigious Proceedings of the National Academy of Sciences, is the first to achieve long-term success in rodents.

The researchers, at BioHybrid Technologies Inc. in Shrewsbury, Mass., are now testing the devices in dogs as well, with preliminary results that look “very successful,” according to BioHybrid President William L. Chick, and could potentially begin human trials in as few as five years.

“This is wonderful,” said biochemist Joan Harmon of the National Institute of Diabetes and Digestive and Kidney Diseases. “These are the best results I have seen so far.”

Type 1 or insulin-dependent diabetes occurs when the body’s immune system destroys insulin-secreting islet cells in the pancreas. Insulin is normally released by the pancreas when the level of sugars in the bloodstream rises after eating. The insulin enables body cells to use the sugars for energy. If the body does not receive insulin, it must use stored carbohydrates for energy. The buildup of toxic byproducts from that process eventually leads to coma and death.

Diabetes is now treated with insulin obtained from cows or pigs or with human insulin produced by genetic engineering techniques. But because it is injected periodically, the levels of blood sugar go through wide variations. Many researchers believe that these concentration swings cause the long-term side effects of diabetes, including nerve damage in the limbs, kidney malfunction and blindness.

Researchers think that the use of a transplanted or artificial pancreas could control those swings and minimize side effects, but they have encountered a number of problems.

Pancreas transplants have had some success; more than 50% of them now survive for 5 years, according to Harmon. But only limited numbers of pancreases are available and they provoke a strong immune response that must be controlled with relatively large doses of immunosuppressive drugs.

Useful insulin pumps that can be implanted in the diabetic’s abdomen have also been developed. These release a slow, steady stream of insulin, supplemented by larger doses after a meal. But because researchers have not yet developed an implantable sensor that can quickly and accurately determine the amount of sugar in the blood, control of sugar levels is still not as precise as would be desirable.

Many researchers have thus pinned their hopes on living islet cells from a donor. Such cells have their own built-in sugar sensors and could thereby provide precise control, releasing insulin only when blood sugar rises. If these cells could be successfully enclosed in a semipermeable plastic membrane, they would be protected from attack by the recipient’s immune system, but still interact with blood.

Unfortunately, Harmon said, the outside of the membranes constructed up to now tended to become overgrown with body cells, thereby choking off the flow of nutrients in, and of insulin out. The islet cells in such chambers thus die within two to four weeks.

The key difference in the new device developed by diabetologist Chick and his colleagues at BioHybrid is the use of a membrane material synthesized by W.R. Grace & Co. of nearby Lexington, Mass. The plastic used in the membrane resists the overgrowth of cells and thus remains unclogged.

Chick said that the devices have been tested for well over 100 days in the rats “with no signs of overgrowth” or clogging. The membranes also have very small passageways through them so that insulin and nutrients can pass through, but not immune cells that would attack the islet cells inside.