Diabetes - Role of Animals

Type 1 diabetes

In Type 1 diabetes insulin-producing cells have been destroyed, which means patients struggle to use energy from the food they eat. They need regular insulin injections for this to take place. Poor utilisation of carbohydrates can also lead to high blood sugar levels and thereafter nerve damage, kidney disease and blindness. Today, monitoring blood sugar levels and regulating them with insulin lowers these risks. There are more than 20 types of insulin products available, each with a different time of onset and duration of action. An individual's lifestyle, physician's preference and experience, and the person's blood sugar levels will influence the choice.

In the days before insulin injections, diabetes was a death sentence. It was a disease with no cure nor treatment, the only management being a diet low in carbohydrates and sugar, but high in fat and protein. This enabled diabetics to live for a few years longer at the most. Today, millions of sufferers are able to control their diabetes thanks to the pioneering work of a team of Canadian researchers: the two best known being Fred Banting and Charles Best.

By 1920, when Banting first became involved, it was already known that there was some connection between diabetes and specialised cells in the pancreas known as the islets of Langerhans. Perhaps in patients the islets were no longer able to deliver some substance that was needed if diabetes is to be avoided. Banting, with his assistant Best, wanted to find out what the islets were making. It was inconceivable that they would extract that substance, whatever it was, from the pancreases of healthy humans.

Once they had got the fluid - now named isletin, later to become insulin - from the pancreases of dogs, they then wanted to know whether it was going to be able to treat diabetes. Again, it would have been quite unethical to give this unknown substance to patients. Instead they created diabetes in dogs and injected them. The treatment worked.

Experiments on dogs continued and a year later Leonard Thompson (a Canadian teenager) became the first person to receive an injection of insulin. For the next 60 years diabetics relied on insulin purified from pigs and cattle. Today it is largely harvested from genetically-engineered bacteria.

The discovery of insulin has saved countless lives and was only made possible by the use of animals. Not only humans have benefited; diabetes also occurs in one out of every 500 dogs and cats. Just like humans, they require insulin shots to control the disease.

Insulin pumps
Insulin pumps, which slowly infuse insulin into the body, better mimic the normal human process. They are good for patients who have trouble controlling their glucose levels. The small pumping devices are worn outside the body. They connect by flexible tubing to a catheter that is located under the skin of the abdomen. The pump is programmed to dispense the necessary small steady doses of insulin. But additional amounts can be given in a short time if needed, such as after a meal. The first pump (CSII) was 'invented' at Guy's Hospital in 1976-77 by Dr John Pickup and was based on the miniature infusion pump developed for infusing parathyroid hormone into dogs and other animals. The subcutaneous insulin pump therapy was first tried in volunteer patients without animal testing but the idea of controlled infusion of hormones at different rates comes from animal studies.

New insulin delivery methods
New methods for delivering insulin include the insulin patch and inhaled insulin. The insulin patch, when placed on the skin, will give a continuous, low dose of insulin. Reduced and stabilised blood sugar levels were observed in diabetic rats for several days following the application of a single patch. To adjust insulin doses before meals, it is envisaged that users will pull off a tab on the patch to release insulin.
Inhaled insulin delivery systems give insulin as a dry power, inhaled through the mouth directly into the lungs where it passes into the bloodstream. Successful human trials follow extensive testing in beagle dogs that helped establish the relationship between the amounts of inhaled insulin and that subsequently circulating in the blood stream.

Islet transplants
The ideal situation for a type I diabetic would be a cure. Islet transplants is one way to achieve this.

The first successful islet transplant operation was performed on laboratory rats in 1972 and cured the animals of their diabetic disorder. The same operation has since been carried out in dogs, in monkeys and ultimately, in 1990, in people. However, until relatively recently this has meant transplant recipients have had to take immune suppressing drugs to prevent rejection of the foreign cells. New approaches that do away with the need for these are currently being trialled in people.

For islet cell transplantation to become a widespread treatment it needs to have a consistent success rate and the requirement for lifelong administration of immuno-suppressive agents must be overcome. There would also need to be many more donors. However, there has already been a significant improvement in the incidence of transplanted islets achieving prolonged insulin production: from 21% in 1990 to 63% today. One way to circumvent these problems is by using a patient's own stem cells and giving them the right treatment so that they turn into islet cells.

Type 2 diabetes

Type 2 diabetics either do not produce quite enough insulin or their cells stop responding to it. Drugs are available to help them manage the disease. Some work by increasing insulin secretion while others reduce the resistance of cells to insulin.

Rats and mice are the most commonly used animals in the study of Type 2 diabetes. Treatments for excess blood sugar (hyperglycaemia), such as cryptolepine and masoprocol were initially tested in the naturally-occurring db/db (diabetic) mouse. This mouse has insufficient insulin secretion and high blood sugar, resulting from a single gene deficiency that leads to insulin resistance - the inability to respond to the insulin signal.

Rats, which are easier to handle than mice and provide larger samples, have been used to look at the mechanism of action of diabetes drugs, their safety and just how well the drugs actually work. Often used are the Zucker diabetic fatty rat and the BB-W rat. Both exhibit excess blood sugar, and are clinically and biologically similar to the diabetic humans. They also enable study of the early development of diabetes and the possible methods of its prevention.

Monitoring blood sugar
Diabetics use a skin prick test several times a day to monitor their blood sugar levels. This can be painful and inconvenient. A possible alternative is an implant that has been tested in the USA on dogs and humans for months at a time. The goal is to provide continuous blood glucose measurements for years on end and have the implant interfacing with an insulin pump. This can be thought of as an artificial pancreas. Already this closed-loop system has controlled glucose levels in dogs for a full week.

A tattoo to warn of dangerously low blood sugar levels is also being tested, this time in rats. Polymer beads coated with fluorescent molecules are injected under the skin, and when glucose levels fall, fluorescence increases.