What is diabetes?
Diabetes is a chronic (long-lasting) auto-immune disease which affects the body’s ability to produce or respond to insulin, stopping the body from processing carbohydrates and resulting in elevated levels of glucose (sugar) in the blood. Over time, excessive blood- sugar levels cause serious damage to many of the body’s core systems, including the heart, blood vessels, eyes, kidneys, and nerves. People with diabetes are at greater risk of developing heart disease and experiencing a stroke.
Symptoms of diabetes include:
- Excessive thirst
- Rapid weight loss
- Excessive urination with high levels of glucose in the urine
How can we treat diabetes?
Before the breakthrough research by Banting and Best that led to the discovery of insulin – research that depended on modelling the disease in dogs – there was no effective treatment for diabetes except for highly restrictive diets containing little or no carbohydrates. Until the introduction of medical insulin in the 1920s, most people that developed diabetes were likely to die within three years. Today, insulin continues to be the most effective treatment for the majority of people with diabetes.
There are two types of commonly occurring diabetes. Type 1, previously known as insulin-dependent, juvenile or childhood-onset diabetes, is caused by a deficiency in insulin production and can be treated with regular insulin injections. Type 2, formerly called non-insulin-dependent or adult-onset diabetes, results from the body’s inability to use insulin effectively and can be treated with oral medication. Some people with type 2 diabetes may also require insulin injections.
Around 90% of people with diabetes have type 2. The causes of type 2 diabetes are complex. Although research indicates that people who are overweight or consume excessive amounts of sugar in their diet are more likely to develop type 2 diabetes, it is unlikely that sugar intake is the only reason the condition develops.
Unfortunately, the number of people with diabetes is increasing and people are developing the condition at an earlier age. Currently, more than 5 million people in the UK are living with diabetes. The World Health Organisation predicts that diabetes will be the 7th largest cause of death in 2030.
Discovering the role of insulin in diabetes through experiments on dogs
The Nobel Prize-winning discovery of insulin in 1921 at the University of Toronto is one of the most spectacular examples of the contribution of animal research to medical progress. Many millions of people with diabetes are alive and well as a result – as are many diabetic dogs.
In the early 1900s, Surgeon Frederick Banting and graduate student Charles Best found that injections of pancreatic cell extracts relieved diabetic symptoms in dogs. The cell extracts contained insulin, which was later identified as the key substance and purified using a technique developed in rabbits.
Before Banting and Best’s experiments, it had already been established that diabetes disrupted the body's ability to metabolise or utilise food, especially carbohydrates and that experimental animals died if their pancreas was removed. The pancreas was thought to hold the key to carbohydrate metabolism, which led to speculation that it might produce a metabolism-promoting substance. Banting, Best and their colleagues John Macleod and James Collin established that this substance existed and gave it the name ‘insulin’.
Thanks to the use of insulin, life expectancy for people with diabetes has increased to more than 77 years for men, and 81 years for women; a stark contrast to 100 years ago, when life expectancy was no more than three years following the development of diabetes.
Read more detail on the experiments that lead to the discovery and application of insulin on animalresearch.info
Other treatments for diabetes that relied on animal research
Islet cell transplantation for type 1 diabetes
From Diabetes UK: “Type 1 diabetes is caused by the destruction of insulin-producing cells in the islets of the pancreas. Islet cell transplantation involves extracting islet cells from the pancreas of a deceased donor and implanting them in the liver of someone with type 1.”
The development of islet cell transplantation to treat diabetes would not have been possible without animal research. This highly technical treatment could not have been developed in humans alone, not without the likelihood of causing undue harm to patients in the process. Islet cell transplantation was perfected in rats, dogs, and later monkeys before moving into human clinical trials.
Patients who receive islet cell transplantations are required to take immunosuppressant drugs to prevent rejection. This is an area that is still undergoing research in animals in order to develop better medicines. In 2022, researchers at Stanford Medicine were successful in using a new three-step approach involving low-dose radiation and antibodies to treat mice using islet cell transplantation, without using immunosuppression.
Gene therapies for type 2 diabetes
In 2013 scientists cured diabetes in dogs using gene therapy, the first time this had been achieved in a large animal. First tested in mice, the treatment delivers functional genes for insulin and glucokinase, which allow the animals to sense and respond to changes in blood sugar levels. The two genes were delivered in viral vectors by injection. Once in the bloodstream, the vectors were absorbed into the animals’ muscle cells where the genes integrated with the genome. Following the gene therapy, the dogs' blood sugar levels were maintained at healthy levels. The health of the dogs was observed for four years without the symptoms of diabetes reoccurring or any adverse side effects being seen.
A gene therapy using the same vector delivery system has already been licensed by the European Medicines Agency, giving hope that patients might not need to wait too long for clinical trials of this new treatment to begin.
Insulin delivery methods developed using animals
Researchers are also looking at new ways of administering insulin, to avoid injections. Insulin pumps slowly infuse insulin into the body and are good for patients who have trouble controlling their glucose levels. The small pumping device, worn outside the body was invented at Guy's Hospital in London and was based on the miniature infusion pump developed for infusing parathyroid hormone into dogs and other animals.
An insulin patch called U-Strip that allows insulin to pass through the skin has been trialled in 100 type-1 diabetes patients, with larger trials expected. The patch relies on a sonic applicator which produces a burst of sound waves that open up the pores of the skin, allowing the insulin to pass through.
Inhaling a dry powder form of insulin is another method of delivery that has been in development in recent years. Testing inhalable insulin delivery in dogs helped establish the relationship between the amounts of insulin inhaled and the amount circulating in the bloodstream. Successful human trials have followed. However, the two leading systems that were put to market – Exubera in 2006 and Afrezza in 2014 – have not seen the uptake that was expected, despite the need for alternative delivery systems to invasive injections.
The artificial pancreas
Researchers from De Montfort University, Leicester, UK are developing a device which could be implanted into the body between the lowest rib and the hip and topped up with insulin every few weeks. Dubbed the ‘artificial pancreas’, the device is currently undergoing pre-clinical trials in rats and pigs. The artificial pancreas is made of a metal casing containing a supply of insulin which is kept in place by a gel. When glucose levels in the body rise, the gel barrier starts to liquefy and releases insulin. The insulin feeds into the veins around the gut and then into the vein to the liver, mimicking the normal process for a person with a healthy pancreas. As the insulin lowers the glucose level in the body, the gel reacts by hardening again and stopping the supply.
Read more on current and historic research into diabetes on AnimalResearch.info
More on diabetes from UAR: