Insulin secretion from beta cells is stimulated in response to high blood glucose concentrations. It acts to lower blood glucose by stimulating uptake of glucose from the blood into cells especially skeletal muscle cells, adipose tissue and liver cells, were it is stored or converted to ATP as an energy source. Insulin also reduces blood glucose by slowing the rate of glycogen breakdown and inhibiting the conversion of fats to sugars. Insulin brings about an anabolic effect allowing dietary sources of glucose to be used to maintain blood glucose whilst preserving the bodies energy stores.
Glucagon is secreted from the alpha cells and has an opposite effect on blood glucose, acting in response to low levels of blood glucose. It activates glycogen phosphorylase in liver, which promotes glycogenolysis, this causes the break down of glycogen stores from liver and muscle cells. Glucagon acts via a cascade mechanism which activates a protein kinase in response to cyclic AMP. This results in the release of glucose and activation of a lipase enzyme, which liberates fat stores in adipose tissue producing fatty acids and ketone bodies.
A potentially deadly disease caused by alteration in protein levels of Insulin is Diabetes Mellitus. This is caused by altered levels of insulin production, resulting from destruction of beta cells in the pancreas. This may result in either depleted levels of insulin secreted from the pancreas, or the alteration of the structure of insulin preventing recognition at insulin receptors. This disease causes, altered carbohydrate metabolism resulting in an uncontrolled increases in blood glucose concentration. The main physiological effect of this disease is that all cells become starved of glucose as a result of the lack of insulin within the blood.
The liver tries to compensate for this lack of glucose within cells by stimulating glycogenolysis and metabolising glycogen stores, resulting in an immediate release of glucose into the blood. This is of little use to the cells, as insulin is not present to allow glucose uptake. The liver then undergoes glyconeogenesis and produces glycocorticoids, resulting in the degradation of muscle proteins. This again causes the release of glucose in the absence of insulin. As the glucose levels within the blood increase the kidney is unable to actively reabsorb the glucose, resulting in excessive amounts of urine containing high concentrations of glucose. The final strategy under taken by the liver is to metabolise fat stores within the adipose tissue. Fat undergoes lipolysis resulting in the synthesis of fatty acids and ketone bodies. Excess levels of ketones due to fat metabolism can cause acidosis, which may result in coma. Ketones and fatty acids are the only sources of energy, which can be utilised by the cells in the absence of Insulin.
Insulin is supplied intravenously in the absence of normal synthesis, enabling the utilisation of glucose by cells. Intravenous administration of insulin can cause a very rapid up take of glucose, this disrupts the homeostasis of the body causing the levels of glucose to fall dramatically. If the concentration of glucose fall less than 2.2mM then Hypoglycaemia occurs, causing a decline in metabolic activity, brain functioning becomes impaired, resulting in coma or possible death. To restore the levels of blood glucose, a substance high in glucose must be consumed. Hyperglycaemia can also cause oedema, this results from non-enzymatic glycosalation. In this case excess glucose from the blood binds to amino groups on proteins within different tissues, resulting in blood leakage damaging cell membranes and therefore cell function. This demonstrates how the alteration of one protein can have a direct effect on others [2]. As the levels of insulin decline the symptoms of diabetes reappears therefore a number of insulin injections are required throughout the day.
Diabetes occurs through a change in a single protein Insulin. Even when the protein is administered in the correct amounts the body is unable to bring about a normal response, this is shown by the effects of Hyperglycaemia. Carbohydrate metabolism demonstrates the importance and diversity of proteins within the body, this is shown through the number of enzymes needed to monitor metabolism and the individual receptors which recognise specific substrates. All of these examples are functioning proteins; alteration in the level of any would potentially have a profound effect on the body.
[1] Campbell and Reece Biological Sciences, 6th Edition, Addison Wesley
[2] http://www.revoptom.com/handbook/sect59a
[3] Martini (2000) Fundamentals of Anatomy and Physiology, 5th Edition
[4] http://www.mediplane.com/Education/Case_Studies/DKa.pdf
