FINDING A SOLUTION:
THE LATEST IN DIABETES RESEARCH
By Zameer U. Baber
April 8, 1996
Insulin is an essential hormone produced by beta cells in the pancreas. Insulin brings glucose into cells, and that sugar can be converted to produce energy, used to produce fats, or stored. Insulin and glucagon carefully control the amount of glucose in the body keeping the blood-glucose level in a narrow range. Thus cells have adequate amount of glucose for energy.
Diabetes is a disorder of metabolism. In type I diabetes, the immune system of the body attacks and destroys the beta cells. The result is that the body produces little or no insulin. A person with type I diabetes must take daily injections of insulin to keep the blood-glucose level at a normal amount. If a person is not treated with insulin, they may have many complications including hypoglycemia, which could develop into life-threatening coma.
Since insulin takes time to react, a person with type I diabetes would have to schedule all meals and time all insulin injections. This is produces a great hassle and isn't easy for patients. Usually someone would have to wait twenty to forty-five minutes after an injection to eat. In 1995, a new fast acting insulin analogue was being tested. This insulin analogue and natural insulin are very similar. The major difference between the two is that the insulin analogue reacts faster with the body. However, the effects of the analogue are shorter. This new insulin takes effect in only five minutes. Thus this would allow a diabetic to eat with little planning. This new insulin analogue has some negative sides to it as well. Since the insulin analogue effects the body for a shorter time, patients would have to inject themselves more often. This could create a more painful inconvenience. Because the insulin analogue starts acting immediately, diabetics would have to eat promptly after the injection. If not, they may develop hypoglycemia. However, a study in Portland has shown that one hundred percent of the people who tried the new insulin analogue would like to continue using it.
Insulin therapy is imperfect. Though it manages the disease, it does not prevent long term complications such as blindness, heart disease, and deterioration of nerves in the hands and feet. These developments could be avoided if the glucose levels were monitored and controlled every minute. However, since injecting insulin does not copy the natural process, it is impossible to control glucose levels at all times.
A new breakthrough was discovered recently with a lot of potential. Dr. Irene Wanke is genetically engineering the liver to perform the functions of the pancreas. She took an insulin producing gene, and attached it to a glucose related part of another gene. Then she injected this into liver cells, where it produced pro-insulin. The pro-insulin is produced in response to the body’s glucose levels. Thus the body can control glucose levels at all times, something that genetic engineering has never been able to achieve. Enzymes from the liver must convert pro-insulin to insulin, similar to how pancreatic enzymes. Though this has not been achieved yet, Dr. Wanke is very close in doing so. This procedure is very promising, and has certainly made a leap towards the solution of diabetes.
In the crusade to end diabetes, doctors have looked for ways to return normal pancreatic functioning to the body. This can be done in many ways including whole pancreas transplants, human islet transplants, animal islet transplants, fetal tissue exchange and creation of artificial beta cells. All of which have positive and negative attributes to them.
Pancreas transplants has always been looked as a possible cure to diabetes. A fully functioning pancreas could make insulin injections obsolete. It also will be able to control blood-sugar levels of the body at all times. This would minimize the chances of getting the severe long term complications of diabetes. However, transplanting an entire pancreas is a complex operation with many set backs. Because the body would reject any foreign tissue, strong immunosupressives drugs would have to be taken. These drugs have very harmful side effects. There is also a shortage of adult pancreases, one thousand diabetics to one pancreas in the United States alone. With the combination of these complications and many more, researchers have looked to find other procedures in finding a cure for diabetes.
Since the islet cells of the pancreas manufacture and secrete insulin, one approach to correct diabetes has been to transplant these cells only. This procedure is less complicated when compared to pancreas transplants. They do not require major surgery, and they can be injected into a vein, where they can move to the liver or other locations. Since the immune system would attack the islet cells, scientists are exploring ways to prevent islet cell rejection. Such immunsupressives as rapamycin and FK506 along with cyclosporine try to prevent rejection with minimal side effects when compared with other immunosuprresives. Other ideas include exposing the new cells with radiation, or treat the cells so they will not trigger the immune system. However, the most promising approach is shielding the islet cells with a membrane. This membrane would allow glucose, oxygen and insulin to pass in and out of the blood stream, but protect the cell from antibodies, and T cells which would destroy the islet cells. In 1993, surgeons were able to successfully transplant islet cells into two people. The result was that these people reduced their insulin dosages and their diabetic complications improved. However, the main obstacle in the way of islet transplantation is a shortage problem. Only one thousand pancreases are available per year, and if only islets are used, three to four pancreases are needed per procedure. Thus the only two hundred and fifty to five hundred people could benefit from islet transplants per year.
The controversial procedure of transplanting fetal pancreatic tissue may be a possible partial solution to diabetes. Human fetal pancreas tissue is easy to culture and can develop and grow once transplanted. The tissue also has the ability to function after it has been frozen and then thawed. All of these factors could help make transplants available to a greater number of people. Using ten to twenty fetal pancreases per one procedure, fetal tissue transplants could cure an additional eight thousand to fifteen thousand people with diabetes. Studies with fetal tissue transplants have shown lowered insulin requirements. However, this procedure did not completely reverse diabetes. In addition the immune system attacked the new pancreases, and the success was short lived. Following the lift of a five year ban on research using fetal tissue from abortions, researchers can further look into this possible aid to help cure diabetes.
Since spare human pancreases are so rare, scientists have looked to other sources. Islet cell transplantation from pig pancreases may be another solution. Pig insulin differs from human insulin by only one gene. Before artificial human insulin, pork insulin was vastly used. Nearly one hundred million pigs are used for food every year thus having ample supply of pig pancreases. However, there is greater rejection with pig islet cells than human cells because in addition to the immune response with human islet cells, other immune devices guard the body from other species. This problem may be overcome by immune isolation techniques, which are now being developed.
Many biotechnology companies have been working on many forms of bioartifical pancreases. BioHybrid Technologies has created a device which contains pig islets which that may be mass produced and implanted into people with diabetes. These devices maintained near-normal blood glucose levels in many dogs and continued to produce insulin up to three and a half years. In 1991, the bioartifical pancreas was about the size of a hockey puck. Now they have evolved to microscopic size, which can be injected by syringe. Neocrin Company is developing a bioartifical pancreas that can be maintained by the body. This company surrounds the islets with a membrane that blocks immune attacks. It also allows new blood vessels to grow up to its surface which would allow blood to feed the islet cells, transport newly formed insulin created by the islets, and dispose of their waste products. Both companies have consulted with the Federal Drug Administration to start clinical testing soon.
Another approach to solving diabetes is to create artificial beta cells which could be produced in an artificial pancreas. Scientists have taken cells from the pituitary glands of mice and genetically changed them so they produced insulin. In addition these cells could react to the rise and fall of blood glucose, similar to normal pancreatic beta cells. Another approach is to change the surface of the beta cells so that the immune system would not recognize them as foreign, allowing them to function without any intervention.
Up until recently, it was uncertain what causes the immune system to destroy insulin producing cells in the pancreas. In 1994, the Children’s Hospital in Pittsburgh announced that they have found strong evidence that a virus is the cause of type I diabetes. The pancreas is very vulnerable to the virus. The immune system over attacks the pancreas to kill the virus. Unfortunately much of the tissue that creates insulin is destroyed in the process. Thus forming type I diabetes. If this hypothesisis true, it could lead to a vaccine for people with family history of diabetes.
In 1995, one of the major proteins that the immune system attack in type one diabetes was identified. Type 1 diabetics produce anti-bodies to many of their proteins. Among these proteins is IA-2, which is found in the pancreas and the brain. Non diabetics have IA-2, and only diabetics have the antibody for it. When the immune system attacks the pancreas, in the initial stages of diabetes, IA-2 is one of the prime targets. Any protein that is a major target for antibodies in diabetics is likely to be related to the disease. The finding could lead to preventing the immune system’s attack on the pancreas and its ability to produce insulin.
As technology and our knowledge of the human body increases, we come closer to finding an answer. What seem like to most obvious solution turns out to be the most hazardous and what seems like something out of a science fiction story may end being the most realistic. As ideas and hypothesis fail, more emerge each sounding more absurd than the last. Whether it is taking an insulin shot or creating a cell based on a pig which is surrounded by a semi-permeable membrane, we are coming closer to finding an answer to one of the most deadliest diseases in existence.
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Zameer Baber is a Junior at St. Paul Academy, in St. Paul, Minnesota (USA). He does not have diabetes. Zameer wrote this research paper about diabetes because he is interested in diabetes.
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