No longer? Researchers hope to replace diabetics' daily injections with pills.

Sticking With It No More

SAN FRANCISCO--For diabetics, life is a constant series of injections to control blood sugar with insulin. That may change, thanks to a new oral form of insulin that can be absorbed through the intestine. The pills have performed well in safety trials but have yet to be tested in a large clinical trial.

The balance of blood sugar and insulin, which cells need to absorb sugar, is a delicate operation. In a healthy person, the liver carefully regulates the flow of insulin and glucose into the bloodstream, keeping levels of both steady. Because their pancreases can't make insulin, diabetics must inject it straight into their bloodstream to keep blood sugar levels from rising too high. In addition to being painful and inconvenient, injections also bypass the liver, delivering insulin directly to muscle cells, which results in fluctuating blood insulin levels. Too much insulin can lead to hypoglycemia and other diabetes-related complications. Because the liver filters everything we eat, insulin taken orally more closely mimics natural insulin regulation. Unfortunately, insulin is easily digested in the stomach and does not penetrate the cells lining the intestinal wall. By chemically modifying the insulin molecule, scientists have apparently jumped this latter hurdle.

The new insulin includes a water-soluble polyethylene glycol chain, allowing the insulin to travel easily in the water-based environments of the intestine and bloodstream. A fat-soluble alkyl group helps the molecule cross the fat-based cell membranes in between. Exactly how it does this is still a matter of speculation, says Christopher Price, president of Nobex Corp. in Research Triangle Park, North Carolina, which developed the compound. Although the modification does not completely prevent digestion in the stomach, it does slow the process, so that some insulin can reach the intestinal wall.

At the annual meeting of the American Association for the Advancement of Science (which publishes ScienceNOW) on 16 February, Price presented data from phase II clinical trials showing that the chemically modified insulin is safe and lowers glucose levels more rapidly than injected insulin does. And research in dogs with diabetes, Price says, has shown that the outfitted molecule controls glucose levels just as well as injected insulin does.

Other researchers advise caution, however. "Oral insulin has been just around the corner for years," says John Patton of Inhale Therapeutic Systems in San Carlos, California, which is developing an inhaled delivery system. "I spent many years studying the intestine. Getting [insulin] across that intestinal membrane and getting [it] absorbed into the body is very tricky business."

Related sites

Nobex Corp.

American Diabetes Association

Inhale Therapeutic Systems

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