Insulin

The Definition of Insulin in Biology

Insulin is one of the main hormones used to regulate blood glucose concentrations within the human body. It acts in concert with the hormone glucagon to maintain blood glucose Homeostasis. The two hormones form a Negative Feedback loop, with insulin lowering blood sugar levels and glucagon raising them. Alternating production of the two hormones results in blood glucose concentrations bouncing up and down within a relatively narrow range on either side of the ideal homeostatic level, usually between 72-99 mg/dL in healthy, fasted individuals. Insulin's role in this cycle is shown in figure 1 below.

Insulin Function

Insulin has a wide array of functions within the body, mainly centring around the lowering of blood glucose. When the pancreas detects increased blood glucose concentration, it begins to secrete insulin into the bloodstream. Once it enters the blood, insulin binds to Receptors on the surface of several types of Cells, mainly fat, muscle and liver Cells. These Receptors then trigger a cascade of chemical reactions which result in glucose being removed from the blood and stored in several ways. For short-term storage of glucose, glucose is stored as glycogen in the liver and muscle cells.

Insulin causes the formation of glycogen initially by triggering glycogenin to bind to glucose molecules using tyrosine residues. These chains are then elongated further by glycogen synthase, which forms further 1-4 glycosidic bonds between glucose molecules. Branching occurs when the glycogen branching enzyme transfers a small chain from the end of the glucose Polymer to a point midway along another glucose branch.

The formed glycogen is then either used locally, as in the case of muscle cells or converted back into glucose and released back into the blood when blood glucose lowers, as in the case of the liver. For long-term storage, insulin acts upon fat cells. Here it triggers the uptake of glucose, followed by its conversion to Fatty Acids. It also increases the rate at which fatty acids are turned into Triglycerides, the long-term storage molecule used in fat cells. The combined action of glycogen and fatty acid synthesis lowers the blood glucose level back towards the ideal optimal level of 72-99 mg/dL in fasted individuals.

Insulin Production

Insulin is produced in beta cells found in the islet of Langerhans, the region of the pancreas that contains its hormone-producing cells. Insulin is formed in several stages within these cells.

Insulin can also be produced artificially as a result of Genetic Engineering. This allows for more efficient insulin production for the treatment of Diabetes than production from animal organs. By extracting the gene for insulin from human DNA, and then inserting it into yeast or Bacteria, scientists can grow large amounts of these organisms and then extract and purify the insulin!

Insulin Secretion

The insulin vesicles are then stored within the beta cells until needed. These vesicles release insulin into the blood via exocytosis. Glucose enters the cell and is converted to ATP, which then closes normally open K⁺ (potassium) channels in the membrane. This then causes a change in the charge of the cell membrane, opening Ca⁺ channels. The resulting calcium influx causes the fusion of the insulin vesicles with the cell membrane. This reaction stops once glucose levels lower to the point that insufficient ATP is produced to keep the K⁺ channels closed.

Insulin Structure

Insulin before undergoing its post-translational modifications is a 110 amine residue-long protein. However, following the removal of various sections, its secreted form is 51 residues long. Before being secreted, insulin is stored in bundles of six within the granule, however, this splits into the active form of single units upon being released from the beta cells.

Insulin Diseases

Insulin is involved in many diseases that affect humans, stemming from either changes in the body's response to insulin or changes in the production of insulin. These diseases include:

• Insulin Resistance Syndrome

• Diabetes

• Insulinoma

• PCOS

Insulin Resistance Syndrome and Symptoms

Insulin resistance syndrome, also known as metabolic syndrome, is commonly seen as a precursor to certain forms of diabetes, mainly type 2. While this was previously thought to be the extent of its effects, it has since been linked to many other diseases including:

• Hypertension

• Hyperlipidaemia

• Fatty Liver Disease

• Atherosclerosis

The mechanisms behind this syndrome and how it links to diabetes are poorly understood, however, it is believed that consistently elevated blood sugar levels result in an overproduction of insulin. Over time the cells within the body, particularly liver, fat and muscle cells, begin to resist or ignore the signals of insulin, requiring larger and larger amounts to be released in order for the same drop in blood glucose levels to occur.

Diabetes

Diabetes is a catch-all name for a variety of conditions, all centring around consistently elevated blood glucose levels, however, the main two are type-1 and type-2 diabetes.

• In type-1 diabetes, the body's Immune System attacks the beta cells within the pancreas, destroying them, thereby lowering or stopping insulin production.

• Type-2 diabetes is a continuation of insulin resistance, where the cells become so resistant to insulin that blood glucose remains consistently elevated. Insulin levels may be increased, decreased or normal, unlike in type-1.

Treatment varies between the two types, with insulin always being necessary for type-1 but only sometimes necessary for type-2 as it can also be managed through the lifestyle changes mentioned above, combined with other oral anti-diabetics.

Insulinoma

An insulinoma is a Tumour in the pancreas formed from beta cells, which secrete insulin into the bloodstream as with regular beta cells. The symptoms caused by this stem from the fact that insulinoma insulin secretion is dysregulated, not responding properly to changes in insulin levels. This results in excessively low blood glucose (hypoglycemia) levels, which will eventually lead to loss of consciousness, seizures and potentially death. Proper blood sugar regulation is usually restored upon surgery to remove the Tumour.

PCOS

PCOS or polycystic ovary syndrome is a syndrome in which a woman's hormone levels are disordered, resulting in the production of excessive levels of male hormones. It is characterised by difficulty becoming pregnant, skipped menstruation, excess hair growth, cramps and many other conditions. PCOS can stem from insulin resistance, with heightened levels of insulin causing increased ovarian testosterone production.