Reading Test - Version 2 Reading Passage B Insulin is still a hard act to swallow Phylida Brown, Research groups around the world are optimistic that they are making progress towards developing the drug insulin in a form that can be taken by mouth, Many diabetics must inject themselves every day with insulin to help control the level of sugar in their blood. For decades, scientists have been looking for an effective way to give people insulin by mouth instead. Insulin is an essential hormone for getting glucose from the bloodstream into body cells, and most people produce it naturally in the pancreas. People with diabetes mellitus produce either not enough insulin or none at all. The hormone cannot normally be taken by mouth because insulin molecules are destroyed by digestive enzymes in the gut. Thus many diabetics must inject them-selves with insulin daily. Researchers have therefore been aiming to package the hormone in some way so that it can survive intact in the gut and cross the gut wall into the bloodstream, ‘The current experiments are all at an early stage. Even if they do lead to an effective treatment, it may not be suitable for every diabetic. Those most likely to benefit are people who find injections difficult, such as blind people and younger children. ‘This month a team in Ohio is applying for permission to test its oral insulin on people. The tablet is a gelatin capsule which contains insulin and a drug similar to aspirin and sodium bicarbonate. The gelatin has a costing of waterproof plastic that becomes permeable in the gut. Murray Saffran, who is leading the research at the Medical College of Ohio in Toledo, says the plastic based on a polymer whose structure contains certain nitrogen- nitrogen bonds known as azo bonds. In the gut, bacteria break down the azo bonds, and the plastic becomes permeable to water. Water enters the capsule and causes a reaction between the aspirin-like drug and the sodium bicarbonate, giving off carbon dioxide and rupturing the capsule, ‘The researchers believe the like drug may also help the insulin to be absorbed. The insulin is absorbed directly from the gut into the vein carrying blood to the liver. Saffran and his colleagues have so far carried out trials of the capsule in rats and - most recently - diabetic dogs. ‘The researchers found that the level of glucose in the animals’ blood fell, on average, from more than 400 to 120 milligrams per decilitre after receiving the capsule. At the same time, the insulin levels in their blood rose, showing they had absorbed the hormone. 18Reading Test - Version 2 Another group has already started testing a different insulin capsule in humans, having first performed animal trials. Hanoch Bar-On and his colleagues at the Hadassah Hospital in Jerusalem have patented their capsule, which is coated so that it is not destroyed by the stomach acid. Bar-On says the capsule contains insulin and “other ingredients” which help to enhance the hormone’s absorption in the gut and to inhibit the enzymes that destroy it. So far, the trial in Jerusalem has been small, involving only eight health volunteers. In future, Bar-on wants to extend the trials to diabetics, but he stresses the need for more research before he can do so. ‘The success of the tests so far has been limited, but encouraging, says Bar-On: in three of the eight, the level of sugar in their blood fell after they took the capsule from 100 milligrams per decilitre to between 80 and 85. At the same time, the insulin level in their blood was seen to rise to a peak then tail off. For the remaining five people, there was no significant effect from the capsule, A third project is led by Yough Cho at Murdoch University in Perth, Australia, together with Cortecs, a company in Isle Worth near London. Cho has devised a combination of insulin and fatty molecules, encapsulated in gelatin. The fatty molecules, which occur naturally in the gut as a product of the digestion of fat, are easily absorbed from the gut and carried to the liver. Insulin attached to these molecules can enter the bloodstream. Cho gave three diabetic men this preparation, in liquid form. In each of the men there was a "substantial reduction” in the level of blood sugar. Their insulin levels were also seen to peak and tail off. The team has published this work in The Lancet (vol ii 1989, p 1518), and clinical trails of the capsule are due to start soon at Guy's Hospital, in London. There are, however, several problems with oral insulin. First, it is relatively inefficient: several times as much insulin is needed to achieve the same drop in blood sugar that a specific amount could achieve if injected. This suggests that a significant amount of insulin is still being destroyed in the gut. Also, the amount of insulin that will be absorbed is unpredictable and can be disrupted, for example, by illness. 19