An estimated million people worldwide suffer waterstones and bestsellers diabetes ANCHOR ,or nearly five per cent of the population, with approximately 3.
Currently eighty per cent of diabetes deaths occur in low- and middle-income countries ANCHORdriving the need for cheaper, easier treatments. Symptoms include raging thirst, rapid weight loss, tiredness and passing large quantities of sugary urine. Type 1 diabetes previously known as insulin-dependent, juvenile or childhood-onset is characterized by deficient insulin production.
Treatment of diabetes involves lowering blood glucose and the levels of other known risk factors that damage blood vessels. People with type 1 diabetes require insulin; people with type 2 diabetes can be treated with oral medication, but may also require insulin. The discovery, isolation and purification of insulin in the s was a significant medical advance, preventing premature deaths in many sufferers.
This was the first demonstration that there was an anti-diabetic factor produced by the pancreas which enabled the body to use sugars in the blood properly, american diabetes association animal testing. This factor was named insulin by Schafer insome years before it was actually identified or isolated through animal testing. There were attempts to produce purer extracts, and two diabetic patients were treated in these trials, but there were similar toxic effects, so the use of such extracts did not continue, american diabetes association animal testing.
Working in Toronto, the surgeon Frederick Banting and medical student Charles Best began american diabetes association animal testing attempts to produce insulin in By the end of that year, american diabetes association animal testing, they had shown in classic animal experiments that pancreatic extracts reduced blood sugar, american diabetes association animal testing, removing sugar from the urine of dogs whose pancreas had been removed ANCHOR.
However, these extracts, once again, produced an unacceptable fever when injected into diabetic patients. He did this using an alcohol extraction technique to produce solutions containing different proteins. To find whether insulin was present in each solution, and in what amount, he measured its activity, monitoring blood sugar levels of rabbits following injection of each solution. Collip developed a measure of activity based on the ability of the extract to lower blood sugar in the rabbit.
Type 1 diabetes, also known as juvenile diabetes, affects people of any age. It is caused by the immune system attacking the insulin-producing cells in the pancreas, although the trigger for this is unknown. The body is unable to regulate blood glucose levels without insulin and so patients must take daily insulin-injections.
If not properly regulated, sufferers can face complications due to irregular blood sugar levels. Low blood sugar levels can lead to seizures and unconsciousness. High blood sugar can cause long-term damage to organs such as the heart and kidneys.
In healthy people, glucose concentrations in the blood increase soon after they eat a meal. As a consequence, beta-cells of the pancreas release insulin, which helps to lower blood glucose levels. Type 2 diabetes can develop when the body cannot produce enough insulin to meet its needs.
This is often triggered by excess body weight and physical inactivity. Many research efforts are focused on finding which mechanisms and biochemical pathways are responsible for triggering this. The hormone helps in the production and release of insulin.
In the past, diabetic patients have been found to be unresponsive to GIP as american diabetes association animal testing as insulin, although it was unclear whether it was a cause or consequence of the disease. By studying the hormone in genetically modified pigs with defective GIP receptors, scientists showed that pigs which could not respond to GIP had fewer beta-cells, resulting in a lower release of insulin.
Inexperiments in mice suggested that the loss of beta cells is not due to cell death but instead due to the cells american diabetes association animal testing back to immature forms ANCHOR. Following the observation that levels of a protein called FoxO1 decrease in beta-cells during early diabetes, researchers created a strain of GM mouse whose beta-cells lack the FoxO1 gene. FoxO1 acts as a sensor of blood sugar levels and responds by activating insulin production. Scientists are also studying animals to better understand how lifestyle factors influence the chances of developing diabetes.
There was also evidence showing signs of dyslipidemia, a condition where abnormally large quantities of fat are found within the body. These results have since been replicated in humans. Researchers found that the human trial volunteers with fructose in their diet had produced new fat cells around vital organs such as the heart and liver. There were also early signs of processing abnormalities which may give rise to heart disease and diabetes.
None of these changes were observed in a group on a glucose-rich diet. AKT is important for glucose transport into cells and for stopping glucose production in the liver. Researchers do not yet know why obese mice form more microRNA than normal mice. This may explain why obesity increases the chances of developing diabetes and understanding this could lead to new treatments for diabetes.
Mice fed on a high-fat diet showed increased levels of free fatty acids in their blood. These interfered with the production of an enzyme GnT-4a involved in making GLUT1 transporters, which allow pancreatic beta cells to monitor sugar levels.
As a result the beta-cells had fewer GLUT1 transporters and the mice showed signs of type 2 diabetes. The scientists looked at beta cells taken from patients with type 2 diabetes and also saw that GnT-4a enzyme production was disrupted, linking their findings in mice to the disease in humans. The impact of diet might not even be observed until the next generation. Rats fed a low protein diet produced offspring that were more likely to develop type-2 diabetes as they grew older ANCHOR.
Offspring of rats fed a low protein diet had lower levels of HNF 4-alpha than those born to normally fed mothers. This decreases the ability of the pancreas to produce insulin and leads to early development of diabetes. HNF 4-alpha levels normally decrease with age, but the poor maternal diet speeds up these ageing effects in offspring.
The nonobese diabetic NOD mouse is a common model used for studying treatments for diabetes. This strain was created by researchers in Japan by selectively breeding the offspring of a laboratory mouse that had spontaneously developed symptoms resembling type 1 diabetes in humans ANCHOR, american diabetes association animal testing.
Since antibodies need to fit very closely to the protein that they target, we cannot always directly apply mouse antibodies to human proteins and vice versa. By breeding NOD mice to produce a certain human protein of interest, e. CD3, researchers can test the effects of the antibody targeting this protein and refine the approach to make it more effective. The symptoms of both the NOD1 mouse and BB rat are due to a complex interplay of many genes, as american diabetes association animal testing seen in humans.
It is the first-line drug of choice for the treatment of type 2 diabetes, particularly in overweight people and those with normal kidney function ANCHOR. InSlotta and Tschesche discovered its sugar-lowering action in rabbits, american diabetes association animal testing, noting it was the most potent of the range of compounds they studied ANCHOR. This result was completely forgotten, as other analogues became popular, which were themselves soon overshadowed by insulin ANCHOR.
Insulin injection Since Banting and Best developed a technique for purifying it sufficiently, insulin injections have saved millions of lives. Diabetics often need to inject themselves with insulin several times a day, as well as taking american diabetes association animal testing viagra and cialis cheap sugar level checks.
The inconvenient and cumbersome nature of this has led american diabetes association animal testing searches for new ways of delivering insulin to the body.
Currently, the only main alternative to injections is an insulin pump, but there are several different approaches that are being developed. Insulin pumps slowly infuse insulin into the body and are good for patients who have trouble controlling their glucose levels. Islet transplants Insulin is normally produced by islet or beta cells in the pancreas, american diabetes association animal testing. Currently, islet transplantation is the only curative therapy for late-stage type 1 diabetes, american diabetes association animal testing.
Successfully carried out in rats, dogs, monkeys and humans, this two tivos and two service plans requires the patient to take immune-suppressants to prevent rejection.
Clinical islet transplantation is also restricted by a severe shortage of donor islets. The video on the right features Dr Aileen King discussing some of her research to improve this process.
Gene therapy Gene therapy may be a way to tackle type 2 diabetes, which tends to hit older, overweight people. In scientists cured diabetes in dogs using gene therapy, the first time this was achieved in a large animal ANCHOR. The treatment delivers functional genes for insulin and glucokinase, american diabetes association animal testing, which allow the dogs to sense and respond to changes in blood sugar levels.
The health of the dogs was followed for four years without the symptoms reoccurring or any adverse side effects. The research team had already shown that the technique worked in mice but needed a more accurate model of human diabetes and so used dogs. 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 Researchers are also looking at new ways of administering insulin to avoid injections. An insulin patch called U-Strip that allows insulin to pass through the skin has been trialled in type 1 diabetes patients, with larger trials expected ANCHOR. The patch relies on a sonic applicator which produces a burst of sound waves that open up the pores of the skin, vicodin and paxil the insulin to pass through. Inhaled insulin delivery systems give insulin as a dry powder, inhaled through the mouth directly into the lungs tplo and cancer american diabetes association animal testing passes into the bloodstream ANCHOR, american diabetes association animal testing.
Extensive testing in dogs helped establish the relationship between the amounts of insulin inhaled and circulating in the bloodstream. Successful human trials have followed. Despite the successful trials, these inhaled systems have not been popular with patients and doctors due to the high cost and bulkiness of the delivery system. Tendon rupture and antibiotics first product to market, Exubera by Pfizer, was withdrawn in because of this and several other companies shutdown their late-stage trials in response.
The artificial pancreas is currently undergoing pre-clinical trials in rats and 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 lets insulin out. The insulin then 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 american diabetes association animal testing by hardening again and stopping the supply. Stem cells It is possible to transplant insulin-producing cells from donors, but sources are rare. Instead, doctors hope one day to be able to grow the specialised cells in the lab from human stem cells.
Human embryonic stem cells hESCs are ideal for this as they can develop into any cell type. They were then transplanted into mice where they developed further into insulin-producing cells, american diabetes association animal testing, curing the mice of type 1 diabetes. Although the research showed that stem cells may one day provide a cure for diabetes, it also revealed hurdles.
For example, some cells developed into bone or cartilage, an unacceptable side-effect that future experiments must resolve before clinical trials are attempted.
After extracting tissue and isolating the stem cells, the researchers exposed the cells to Wnt3a — a human protein that switches on insulin production — and also to an antibody that blocks a pulse and blood pressure variation inhibitor of insulin production.
Within a week, insulin and glucose levels in treated rats matched those in non-diabetic rats. Later, when the sheets of cells were removed from the pancreas, american diabetes association animal testing, the diabetes returned.
In addition, fewer beta cells died in treated animals compared to untreated controls. The hormone acts in a similar way to glucagon-like peptide-1, which is already american diabetes association animal testing by existing type 2 diabetes drugs.