5.4.4 Diabetes

• There are over 3 million people suffering from diabetes in the UK
• Diabetes is a condition in which the homeostatic control of blood glucose has failed or deteriorated
• In individuals with diabetes their insulin function is disrupted which allows the glucose concentration in the blood to rise
  • The kidneys are unable to filter out this excess glucose in the blood and so it often appears in the urine
  • The increased glucose concentration also causes the kidneys to produce large quantities of urine, making the individual feel thirsty due to dehydration

• There are two different types of diabetes: type I and type II

Type I diabetes

• Type 1 diabetes is a condition in which the pancreas fails to produce sufficient insulin to control blood glucose levels
• It normally begins in childhood due to an autoimmune response whereby the body’s immune system (T cells) attacks the β cells of the islets of Langerhans in the pancreas
  • The β cells detect high blood sugar and synthesise insulin

• The lack of insulin also affects glycogen stores which results in an individual feeling fatigued
• If the blood glucose concentration reaches a dangerously high level after a meal then organ damage can occur
• Type 1 diabetes is normally treated with regular blood tests, insulin injections and a diabetes appropriate diet
  • Health authorities encourage diabetics to eat a similar diet to the general public. They suggest five portions of fruit and veg a day, minimally processed food and consuming more polysaccharides than monosaccharides or disaccharides

• The insulin used by diabetics can be fast-acting or slow-acting; each allowing for a different level of control
• If a type I diabetic manages their condition well they can live a very full life

Type II diabetes

• Type II diabetes is more common than type I
• It usually develops in those aged 40 and over however more and more young people are developing the condition
• In type II diabetes the pancreas still produces insulin but the receptors have reduced in number or no longer respond to it
  • This reduced sensitivity to insulin occurs in the liver and fat storage tissues

• The lack of response to insulin means there is a reduced glucose uptake which leads to an uncontrolled high blood glucose concentration
  • This can cause the β cells to produce larger amounts of insulin which ultimately damages them

• For early-stage type II diabetes, a sugar and fat controlled diet and an exercise regime are usually sufficient treatments
  • Any food that is rapidly digested into sugar will cause a sudden, dangerous spike in blood sugar

• There are several known risk factors for type 2 diabetes:
  • Obesity
  • Physical inactivity
  • High blood pressure
  • High blood cholesterol

• Genetics seems to be another influencing factor for developing type 2 diabetes
  • Having a relative with type 2 diabetes makes an individual more likely to develop it
  • Specific ethnic groups are more likely to develop the condition

Type I diabetes and type II diabetes

Diabetes and blood pressure

• Individuals with poorly controlled diabetes often suffer from high blood pressure
• The high blood glucose concentration lowers the water potential of the blood which causes more water to move from the tissues into the blood vessels by osmosis
• As a result, there is a larger volume of blood within the circulatory system which causes blood pressure to increase

Producing insulin using GM bacteria

• DNA that has been altered by introducing nucleotides from another source is called recombinant DNA (rDNA)
• If the organism contains nucleotides from a different species it is called a transgenic organism
• Any organism that has introduced genetic material is a genetically modified organism (GMO)
• Recombinant DNA has been used to produce recombinant proteins (RP), thus recombinant proteins are manipulated forms of the original protein
• Recombinant proteins are generated using microorganisms such as bacteria, yeast, or animal cells in culture. They are used for research purposes and for treatments (eg. diabetes, cancer, infectious diseases, haemophilia)
• Most recombinant human proteins are produced using eukaryotic cells (eg. yeast, or animal cells in culture) rather than using prokaryotic cells, as these cells will carry out the post-translational modification (due to the presence of Golgi Apparatus and/or enzymes) that is required to produce a suitable human protein
• In 1982, insulin was the first recombinant human protein to be approved for use in diabetes treatment
• Bacteria plasmids are modified to include the human insulin gene
  • Restriction endonucleases are used to cut open plasmids and DNA ligase is used to splice the plasmid and human DNA together

• These recombinant plasmids are then inserted into Escherichia coli by transformation (bath of calcium ions and then heat or electric shock)
• Once the transgenic bacteria are identified (by markers), they are isolated, purified and placed into fermenters that provide optimal conditions
• The transgenic bacteria multiply by binary fission and express the human protein - insulin, which is eventually extracted and purified
• The advantages for scientists to use recombinant insulin are:
  • It is identical to human insulin unless modified to have different properties (eg. act faster, which is useful for taking immediately after a meal or to act more slowly)
  • There is a reliable supply available to meet demand (no need to depend on the availability of meat stock)
  • Fewer ethical, moral or religious concerns (proteins are not extracted from cows or pigs)
  • Fewer rejection problems or side effects or allergic reactions
  • Cheaper to produce in large volumes
  • It is useful for people who have animal insulin tolerance

Producing insulin using stem cells

• Currently, there is no cure for diabetes but there is ongoing research to see if stem cells could be the answer
• Stem cells can be treated so that they differentiate into pancreatic β cells
• These newly developed β cells can then be transplanted into the pancreas of a diabetic individual, replacing the damaged cells and allowing them to produce insulin
• The early-stage research has had some success using mice as model animals however it has not yet advanced to human trials