Insulin: A hormone synthesised by the beta cells of islets of Langerhans - key to regulating carbohydrate and fat metabolism in the body.    

Since the remarkable power of insulin was discovered in 1922 – millions of people across the world have had their health and wellbeing restored. 

The Basics:

The body is under constant battle to maintain the delicate balance between blood glucose levels and glycogen storage in the liver and muscle. Insulin plays a pivotal role in regulating a negative feedback loop. When glucose levels rise, insulin is released, causing glucagon to become inhibited. When glucose levels drop below threshold, insulin is not released and therefore fat is used as an energy source or gluconeogenesis occurs.

Diabetes Mellitus occurs as a consequence of a defeciency or a hyporesponsiveness to insulin. With an absence of insulin in the islets of langerhans there is no internal source of insulin -  therefore survival of patients with Type 1 Diabetes rests upon insulin injections, (the hormone cannot be given orally due to denaturing gastrointestinal enzymes see treatment)

Other functions of insulin include:

• Control of signalling to other body systems.
• Vascular compliance
• Cognition ( Enhances learning and memory, verbal memory in particular)

Up regulating brain insulin signalling via intranasal insulin administration can elevate the acute thermoregulatory and glucoregulatory response to food intake. This has lead to research into how the central nervous insulin contributes to the control of energy homeostasis in humans.

Sterotypical Blood Glucose Levels during a 24 hours period.
 

 Fluctuating blood sugar levels in correlation to insulin levels, (in humans) over a 24 hour period in which 3 meals are consumed. The effect of a sugar-rich versus a starch-rich meal are also shown on the graph.(Solimena Lab and Review Suckale Solimena 2008 Frontiers in Bioscience)

A Molecular look at Insulin:

• It is a peptide hormone
• It has a precursor: proinsulin encoded by the INS gene
• It is composed of 51 amino acids.
• A strong homology can be seen in the insulin sequence across a diverse range of species due to stong conservation.

- differs from bovine insulin by just 3 amino acid residues.

- differs from porcine insulin by just 1 amino acid residue.

Insulin Storage:

Insulin is produced and stored in the body as a very stable inactive hexamer - while the active form is the monomer. The hexamer-monomer conversion underpins insulin formulations for injection. The monomer displays a rapid response as its diffusion rate is inversely related to particle size. A fast-reacting drug like insulin gives diabetics more flexibility in their daily schedules as it doesn't have to be injected hours before mealtimes. However Insulin can aggregate and form fibrillar interdigitated beta-sheets – causing injection amyloidosis.

Insulin Release:

Beta cells in the islets of Langerhans release insulin in two phases.
1. Rapid release in response to increased blood glucose levels.
2. Sustained, slow release of newly formed vesicles triggered independently of sugar. Other triggers: Amino Acids, parasympathetic nervous system and alterations in the β-cell's membrane potential. e.g. acetylcholine triggers the relase via Phospholipase C.

Insulin release from the pancreas is not continuous, but oscillates with a period of 3–6 minutes. This alters the blood insulin concentration from 800 pmol/l to less than 100 pmol/l. Current research shows this oscillation prevents down-regulation of insulin receptors in target cells as well as assisting the liver in extracting insulin from the blood. Pharmacological research is constantly aiming to create a drug that imitates this endogenous oscillation: there are currently two proposed methods:

• Delivering insulin rhythmically to the portal vein
• Islet cell transplantation to the liver.

Insulin's Rapid Life:

An endogenous insulin molecule will be degraded within 60 minutes of being released from the pancreatic beta cells. This is mainly achieved by the liver although the kidney also helps out in the systemic circulation. Degradation normally involves endocytosis of the insulin-receptor complex along with an insulin degrading enzyme.

 There are 2 groups in which therapeutic Insulin can be categorised displayed in the table below:

Forms of therapeutic Insulin 

Currently the most widely used form is human insulin and insulin analogues, however some patients continue to use animal forms. The use of insulin must be tailored in attempt to gain the best possible control and to minimise the risk of disabling hypoglycaemia.

 Forms of Insulin – based on pharmokinetics.

 For more information on treatment of diabetes please click this link : Treatment of Diabetes

Incretin mimetic - A non-insulin medication specific to patients with Type 2 diabetes.

Two types: Exenatide and Liraglutide.

Mechanism of action: increases the level of the incretin hormone in the blood system to aid in:

•  reducing the metabolic rate

• regulation of insulin and glucose levels depending on the state of the body’s blood glucose levels.

Diabetes is not the only disease caused by defective Insulin release, other pathologies include:

• Insulinoma
• Metabolic syndrome
• Polycystic ovary syndrome