Diabetes (Advanced Level)

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Insulin preparations

Insulin is a 51 amino acid protein and needs to be injected into the body rather than taken orally to avoid being broken down in the digestive system.

Early insulin treatments used the hormone isolated from cow (bovine) and pig (porcine) pancreas. This needed a great deal of purification to isolate the insulin and even then, there were contaminants. The preparations were short-acting and could cause allergic reactions.

In 1955, the amino acid sequence of human insulin was discovered. The amino acid sequence of porcine insulin is different to human insulin by one amino acid. Bovine insulin differs by three amino acids.

Modern insulin is now obtained from bacteria that have been genetically modified to produce human insulin. By further manipulating the insulin, it has been possible to develop a range of medications that have different properties. For example, adding zinc causes the insulin molecules to form hexamers (six insulin molecules loosely attached to each other). This form of insulin is absorbed into the body more slowly than regular insulin, thus reducing the need for more frequent insulin injections.

Range of insulin preparations, from short acting to long acting.

New Treatments

Injecting insulin on a regular basis can cause problems and researchers are constantly working to develop better ways to take insulin.

Skin patches are being developed that allow the insulin to be directly absorbed into the body and implants under the skin may also be a treatment of the future.

Small pumps which inject insulin under the skin in a controlled way throughout the day are now available. Miniaturised 'nanopumps' may soon replace the large pump shown here.

Pumps deliver controlled amounts throughout the day.

Using nanopumps may allow insulin to be delivered from pumps the size of skin patches.

Courtesy of: Insulin Nanopump&#8482 from Debiotech SA, Switzerland

Inhaled insulin-powders have been developed to enable the hormone to be absorbed directly into the blood from the nose and mouth mucosa. This bypasses the digestive system. These have so far proved unpopular with patients and their use is limited.

Transplants of the pancreas and islet cells from donors are becoming more common treatments. People with diabetes, particularly if they have associated kidney disease that requires a kidney transplant, may be given a whole pancreas from a donor. More commonly people with diabetes may be given donor islet cells. These donor cells are isolated from the several donors and then injected into the hepatic vein. From here they travel in the blood and become lodged within the liver and produce insulin. This procedure is called islet cell embolisation. As a result of both of these procedures insulin production in individuals with type 1 diabetes is reinstated and they no longer have to inject insulin.

In the future it may be possible to grow large numbers of beta cells from stem cells in the laboratory. This would be a much more readily available supply of insulin-producing beta cells which can then be used for islet cell embolisation.

Treating type 2 diabetes

Lifestyle changes play a key role in the management of type 2 diabetes, and initial steps include regular physical activity, a balanced diet and loss of any excess weight. For a large proportion of people with type 2 diabetes changes to their lifestyle will reduce their blood glucose levels sufficiently. However if levels remain high even with these changes, then medication is usually required.

There are five types of medicines that are used to treat type 2 diabetes. However, these should be used in addition to a change in lifestyle. The groups of medicines are:

Metformin
Acts on the liver to reduce the production of glucose from fatty acids. Increases the uptake of glucose by skeletal muscle. Protects cells lining the blood vessels from damage and so reduces cardiovascular disease.
Sulphonylureas and Meglitinides
Bind to receptors on the beta cells in the pancreas and promote insulin release.
Acarbose
Inhibits the enzyme that breaks down polysaccharides in the diet and so slows the absorption of glucose in the small intestine to prevent the glucose peak after a meal.
Gliatazones
Increases the sensitivity of fat, liver and muscle cells to insulin.

Long acting insulin may, if necessary, be administered once a day.

Question 4

Compare and contrast the treatment of type 1 and type 2 diabetes. Highlight the reasons behind using each type of treatment.

Click to see what our expert thinks

Acarbose

This type 2 diabetes medication is not much used now.

Amino acids

The basic building blocks of proteins. There are twenty amino acids used, in different combinations, to make every protein required by the human body.

ATP (adenosine triphosphate)

A small organic non-protein molecule that is a source of chemical energy within a cell.

Autoimmune disease

A disorder where the body's immune system behaves abnormally and starts attacking its own cells

Autopsies

The study of the human body to investigate how a disease or injury leads to death

Cardiovascular disorders

Diseases linked to the heart and its blood vessels, for example heart disease and stroke

Diabetic ketoacidosis (DKA)

When glucose is high in the blood but unable to enter cells, the body starts using stores of fat for energy, which results in the production of acidic ketones as a by-product. If ketone levels rise unchecked a hyperglycaemic coma can result which may be fatal.

Disulfide bridge

A covalent S-S bond that joins two cysteine amino acids together, also called an SS-bond or disulfide bond.

Duodenum

Within the human body this is the first 25 - 30cm long section of the small intestine.

Embryo

The name for a group of cells that are developing into a foetus. In humans this is from implantation to the 8th week of development

Endocrine gland

A gland which secretes hormones straight into the bloodstream rather into the blood via a tube or duct.

Enzyme

Biological catalysts that speed up chemical reactions.

Exocrine cells

Cells found in the exocrine glands that secrete hormones into ducts, as opposed to straight into the bloodstream.

Fermentation

Process where microorganisms are cultured so that they reproduce and increase in quantity

Fatty acid

Large molecule consisting of a carboxylic acid (RCOOH) with the 'R' being a long unbranched hydrocarbon chain.

Gastrointestinal

Relating to the body's digestive system, including the stomach and intestines.

Gene

A short piece of DNA which is responsible for the inheritance of a particular characteristic. It codes for the production of a specific protein

Gene therapy

A new, experimental method of fighting disease by replacing a defective gene with a healthy gene

Genetic engineering

A general name for the processes which scientists use to produce desired characteristics or substances that are in short supply, such as human insulin

Glucagon

A hormone produced by the pancreas. It causes the liver to convert glycogen back to glucose and to release glucose into the bloodstream.

Glucose

A type of sugar: a monosaccharide with 6 carbon atoms (a hexose sugar)

Glycogen

A polysaccharide,
(C ₆ H ₁₀ O ₅ ) _n , that is stored in the liver and in muscles and can be converted back into glucose when needed by the body.

Harvested

The process by which a useful substance is extracted

Home Office

The UK government department responsible for regulating the use of animals in scientific research

Hormone

A chemical messenger produced by a particular gland or cells of the endocrine system. Hormones are transported throughout the body in the blood stream but they produce a response only in specific target cells

Hydrogen bond

An intermolecular force between hydrogen, when it is covalently bonded to a highly electronegative atom (fluorine, oxygen or nitrogen), and an oxygen, nitrogen or fluorine atom on another molecule.

Hyperglycaemic

This is the term used when the blood glucose level is too high (more than 10 mmol/l)

Hypoglycaemic

This is the term used when the blood glucose level is too low (less than 4 mmol/l)

Immune system

The body's own system for protecting it against disease (where it produces antibodies to attack invading pathogens)

In vitro fertilisation

A process where the egg is fertilised outside of the body and then transferred back into the uterus to develop normally

Insulin

A hormone produced by the pancreas. It is active in controlling blood glucose levels as it allows cells in the body to take in and store glucose.

Liver

A large organ in the upper abdomen which manufactures, stores and breaks down substances as required by the body

Mitochondria

Organelles within cells that produce ATP, used as a store of chemical energy. Often called the cell's powerhouse.

Mucosa

The membrane that lines the body's cavities and passages. In certain areas, such as the nose and mouth, this membrane absorbs substances and secretes mucus.

Non-animal alternatives

Processes such as cell culture, computer modelling, imaging and microdosing of human volunteers that can give information on potential harmful effects of a substance

Obesity

A disorder where an excessive amount of fat has accumulated in the body. It results when the energy taken in as food is stored in the body instead of being used up through activity

Organelles

A distinct part of the cell, such as the nucleus, ribosome or mitochondrion, which has structure and function.

Pancreas

An endocrine gland which produces insulin

Polysaccharides

Complex carbohydrates consisting of more than one sugar molecule.

Proteins

A polymer made up of amino acids joined by peptide bonds. The amino acids present and the order in which they occur vary from one protein to another.

Receptors

Protein molecules attached to cells that only bind to specific molecules with a particular structure.

Respiration

The biochemical process by which the cells in the body release energy

Messenger RNA (ribonucleic acid)

Single chains of nucleotide units that transmit the information from the DNA inside the cell's nucleus to the ribosomes in the cytoplasm which synthesise the required proteins.

Ribosome

Small organelles that synthesise proteins.

Rough endoplasmic reticulum

A network of membranes within a cell which has ribosomes attached to it. They are important in the synthesis and transportation of proteins.

Stem cells

Undifferentiated cells that can develop into a diverse range of specialised cell types.

Sterile

Uncontaminated by microorganisms

Triglycerides

The most common lipid found in nature and consists of a single glycerol molecule bonded to three fatty acids.

UK Law [for animal testing]

Animal welfare is regulated in the UK by the Animal (Scientific Procedures) Act 1986

Vesicle

A small sac that stores or transports substances inside a cell.

X-ray crystallography

A technique that uses the diffraction of X-rays to determine the molecular structure of a crystalline substance.