The first part of this two-part series of articles deals with the biotech perspective of the etiology of diabetes. Also included is a descriptive on non-drug therapies to treat diabetes like transplantation of pancreas and replacement of islet cells.

Diabetes as a disease is fairly widespread. It is a complicated disease especially as it affects younger as well as older people alike. More people die of diabetes than either breast cancer or AIDS. In the US it is the seventh leading cause of death.

People with diabetes have very high levels of blood sugar. This could result in heart and kidney problems, stroke, blindness and other illnesses.

The islet cells of the pancreas are responsible for producing insulin. When the islet cells gets destroyed diabetes occurs. As a matter of fact, in the case of a person with diabetes his own immune system is responsible for destroying the insulin producing pancreatic islet cells.

There are two different types of diabetes namely:

• Type 1: This type of diabetes occurs when the islet cells of the pancreas are viewed as foreign cells by the body's immune system and therefore destroyed. Type 1 typically affects children, adolescents and younger adults. When the islet cells get destroyed the production of insulin comes to a halt. Without insulin glucose starts building up in the blood stream as it cannot enter the cells.

• Type 2: This type of diabetes occurs when the body cannot use insulin due to what is called insulin resistance and it typically affects the older and overweight people especially those having a sedentary lifestyle. Nevertheless, type 2 diabetes also results in excess blood sugar. This type of diabetes typically does not need insulin injections. Proper diet, exercise and some medications will suffice. Nonetheless, type 2 diabetes could also eventually lead to a situation that only insulin could lower the blood sugar levels.

There are different therapies for diabetes. But to understand these therapies, especially cell based therapies for diabetes, one must know the basics of the different types of cells in the pancreas.

Mammalian pancreas has three types of cells:

• Ductal cells~ these cells connect the acinar cells to the digestive system and are found in the pancreatic ducts. Some researchers believe that ductal cells can differentiate into islet precursor cells.

• Acinar cells~ these cells produce digestive enzymes.

That apart, in human beings the pancreas is a constituent of the small intestine as it is believed to be an extension of the duodenum. Some researchers believe adult stem cells can be found in the pancreas while others don't think so.

The islet cells which are part of the endocrine system and the acinar cells have their origin from the ductal cells. As they develop, these islet cells come out of the pancreatic ducts and gather together to form what are called islets of Langerhans.

There are four types of islet cells namely:

• Beta cells that produce insulin (constitute 65-90% of all islet cells in humans)
• Glucagon producing alpha cells (constitute 15-20% of all islet cells in humans)
• Somatostatin producing delta cells (constitute 3-10% of all islet cells in humans)
• Pancreatic polypeptide producing PP cells (constitute 1% of all islet cells in humans)

Each of the hormones produced by these islet cells have a role in regulating the hormones produced by other islet cells. How islet cells are formed right from birth into adulthood is not yet fully understood. For instance, some researchers even believe that new islet cells are produced from stem cells in the blood.

Treatment of diabetes

It is evident that diabetes has no permanent cure. In other words, although there are several drugs to treat diabetes there is no such thing as a uniformly effective therapy as yet.

Why is that so? For example, people with type 1 diabetes have to take insulin injections several times a day throughout their lives with constant monitoring of their blood sugar levels every day. If they succeed in controlling the blood sugar levels they could avoid some other diseases like heart problems and blindness.

Newer therapies for diabetes other than drugs

Apart from research for newer drugs to treat diabetes other areas of research has been focused on:

1. Transplantation of pancreas
2. Replacement of islet cells

The basis of both these treatment paradigms is the fact that if destroyed insulin producing pancreatic islet cells could be replaced one way or the other it could become a possible cure for diabetes.

Transplantation of pancreas

Transplant of pancreas is not a popular method of treating type 1 diabetes especially as the availability of transplantable pancreas is less. But it has more than 75% success rate. Not only that, people with transplanted pancreas has to take immune-suppressant medicines throughout their remaining lives. This means they could be prone to other illnesses as suppression of one's immune system is probably a greater danger than diabetes itself.

Replacement of islet cells

Doctors have tried to graft islet cells of the pancreas as a possible method to cure diabetes since the islet cells are responsible for the secretion of insulin and other hormones. These islet cells are usually obtained from cadavers. Every transplant requires at least islet cells from two cadavers which had not been dead for more than eight hours. That apart, the tissues must match the recipients' tissue and must be compatible from an immunological point of view. But here again immunosuppressant therapy was essential to prevent rejection of the grafted islet cells. The steroids that are injected as part of immunosuppressant therapy could harm the islet cells. So this method of transplanting islet cells hasn't been reckoned as successful because the patient still faces threat from other illnesses.

However, there is a variant of this procedure which is called the Edmonton protocol. This procedure involves transplanting greater amounts of islet cells together with a proprietary immunosuppressant therapy. Interestingly, the Edmonton protocol has been found to be reasonably successful.

In the next article we will discuss cell based therapies for treatment of diabetes.

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