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					                                                   Insulin:
                                    The story of medicine development
                            (including details of a simple practical experiment)

Diabetes mellitus affects around 150 million people around the world. There are two main types of
diabetes mellitus. Type 1 diabetes often starts in very young people and is due to absence of a hormone
called insulin that is normally produced by the pancreas and that keeps the amount of sugar (glucose) in
the blood under control. In type 1 diabetes the body’s immune system destroys the cells that produce
insulin. The much more common type 2 diabetes typically starts in older people and is due to the combined
effect of a reduced production of insulin and a reduced action of insulin in the body. All patients with Type
1 diabetes require daily injections of insulin, without which they will die. Many patients with type 2
diabetes also need insulin injections, although there are also medicines in tablet form that can help many of
these patients. Insulin has saved countless lives and it is estimated that, worldwide, there are 15 million
people alive today who owe their lives to the discovery of insulin. However, it must be injected and, even
with insulin treatment, the blood sugar concentration is difficult to control perfectly. Due to imperfect
blood sugar control, many patients with diabetes still suffer long term complications, which can result in
blindness, kidney failure and damage to nerves. Thus research continues to better understand what goes
wrong in patients with diabetes and to develop new, better and more convenient treatments.

HISTORY:
     1500 BC. The earliest recorded symptoms of the disease were described in the Ebers Papyrus of
       Egypt.
     150 AD. Arataeus of Cappadocia was the healer who gave the disease its name – diabetes, which
       is from the Greek word meaning to “flow through a siphon” and relates to the large amount of
       urine produced by patients with untreated diabetes.
     6th Century AD. Hindu physicians noted that the urine of patients with this disease tasted sweet.
     18th Century AD. It was discovered that the sweet taste was due to the presence in the urine of the
       sugar glucose. The disease now became known as diabetes mellitus, where “mellitus” refers to the
       sweet (“honeyed”) taste.
     1889. Two German scientists, Josef von Mering and Oskar Minkowski, showed that dogs
       developed diabetes mellitus when the pancreas was removed and suggested that the pancreas
       produced a substance that regulated the amount of glucose in the blood.
     1894. Edouard Laguesse suggested that the small groups of cells scattered throughout the
       pancreas and identified years before by Paul Langerhans were the likely structures to produce the
       substance that regulated glucose and named them the islets of Langerhans.
     1900. Eugene Opie suggested the link between the islets of Langerhans and diabetes
     1909. Jean de Meyer suggested that the substance produced by these islets should be called
       insuline. Many people tried in vain to extract this substance from the pancreas. We now know
       that the difficulty was due the massive destruction of insulin during the extraction process by
       digestive enzymes present in the pancreas.
     1921. Frederick Banting and Charles Best, working in Toronto in the laboratory of John J.R.
       Macleod, overcame these problems and produced the first consistently successful insulin
        preparation. They achieved this by tying off the pancreatic duct, which resulted in the
        degeneration of the part of the pancreas producing the digestive enzymes, without influencing the
        cells that produced insulin. This allowed insulin to be extracted without being destroyed. They
        successfully treated dogs with diabetes and then purified insulin with the help of a chemist, James
        Collip, so that they could treat fourteen-year-old Leonard Thompson who was dying from
        diabetes. The results were dramatic and Leonard recovered.
       1923. Banting and Mcleod were awarded the Nobel Prize for Medicine and Physiology and shared
        their prize money with Best and Collip.

How do scientists discover new treatments for diabetes?
        They devise experiments to understand what goes wrong in diabetes. This is essential to
           devise better ways of treating and even preventing the disease. Much of this work requires
           the use of normal animals (mostly rats and mice) and animals with diabetes. Experimental
           animals can now be made diabetic using chemicals that destroy the insulin secreting cells.
           There are also rats and mice that develop diabetes spontaneously. These animals, just like
           those used by Von Mering, Minkowski, Banting and Best, continue to provide invaluable
           information that has allowed the development and testing of better forms of insulin and the
           development of new medicines that can be taken by mouth to treat patients with Type 2
           diabetes.
        They synthesise new drugs for lowering blood glucose. These are tested in various systems
           including
                o Cells in culture
                o Cells obtained from animals
                o Cells obtained from humans
                o Normal animals
                o Animals with diabetes.
        Once effective treatments are identified and shown to be safe in toxicity tests (again using
           cells in culture and cells obtained from animals and normal animals) tests (called clinical trials)
           are carried out in humans. The first tests are performed in normal, healthy volunteers and
           finally performed in large-scale studies in patients with diabetes.
        When these studies are complete and have demonstrated that the medicine works and is safe,
           the medicine may be licensed by the appropriate authorities so that it can be used to treat
           patients. It takes on average 10-12 years to develop a new medicine and costs around £350
           million. Medicines licensed in the UK in recent years for treating Type 2 diabetes include
           repaglinide, nateglinide, rosiglitazone and pioglitazone.
A simple experiment: Test for glucose

Glucose is not normally present in the urine because the kidneys are very effective in keeping glucose in the
blood. However, when the amount of glucose in the blood increases to the levels seen in untreated
diabetes glucose appears in the urine and this forms the basis of one of the tests used in the diagnosis of
diabetes. The test for glucose in urine is mimicked in this experiment.

Materials needed

1 box of Clinistix Reagent Strips (available from pharmacies- about £5.00 for 50 strips)
Solutions of glucose (0, 0.5%, 1%, 2%)
Clean plastic containers

Procedure

   i.   Remove one reagent strip from bottle and close bottle. Avoid touching the pink tip of the strip.
  ii.   Dip the pink tip of the strip in the solution containing no glucose and remove immediately
 iii.   Draw the edge of the strip against the side of the container to remove excess liquid
 iv.    Compare the test area of the strip with the colour chart on the side of the bottle exactly 10 seconds
        after wetting. Hold the strip close to the colour blocks and match carefully.
  v.    Record the result as “negative”, “light”, “medium” or “dark”
 vi.    Repeat for the other solutions using a fresh strip for each solution

Note: it is very important a) to wash your hands before opening the Clinistix container and handling the
strip and b) not to touch the pink end of the strip. Why?

Further reading: Do a computer search for diabetes e.g.
http://health.yahoo.com/health/centers/diabetes/2.html
Other interesting internet sites
Insulin: History of a discovery
http://www.aventis.com/future/downloads/PDF/fut0203/En_03_2002_the_discovery_of_insulin.pdf
Doctor over time – an interactive diagnosis game (illustrates advances in treatment from 1900-1998)
http://www.pbs.org/wgbh/aso/tryit/doctor/
NOTE: Practical work should always be undertaken with due regard to the appropriate health and safety
precautions.

				
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posted:10/18/2012
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