- Why should I care about diabetes?
- Why is diabetes fatal if untreated?
- What is insulin and where does it come from?
- What are the Islets of Langerhans?
- What is glycogen?
- What is the difference between Type 1 and Type 2 diabetes mellitus?
- What is known about the insulin receptor?
- What is the structure of insulin?
- Why does the breath of an untreated diabetic smell of acetone (nail varnish remover)?
Do injections of insulin really cure Type 1 diabetes mellitus?
Why should I care about diabetes?
Diabetes mellitus remains the third leading cause of death in the USA after heart disease and cancer! Most families are impacted by this disease either through a family member, or by a friend of the family.
Why is diabetes fatal if untreated?
In this disease, the levels of glucose in the blood are not controlled adequately. In particular, glucose levels become elevated from normal concentrations, leading to the excretion of this key energy source in the urine. More importantly, cells cannot make use of the increased amounts of glucose in the blood, and so energy generation pathways cannot operate properly. As glucose is the only energy source that can be used by nerve cells, brain function is severely impaired. The lack of glucose within the cells then leads to increased metabolism of fatty acids and the molecules that are used to make cell membranes, resulting in the formation of "ketone bodies" which decrease the acidity of the blood. In turn, the kidney excretes the excess acid but in so doing, essential minerals like sodium, potassium and phosphate ions are also lost from the body. Excretion of these materials requires large volumes of water and, for this and a number of other reasons, the blood volume becomes severely decreased even if the diabetic drinks large quantities of water. This raises the blood pressure, because the blood becomes very viscous (especially as there is so much glucose present), straining the heart and also damaging the kidneys.
What is insulin and where does it come from?
How does insulin control the levels of glucose in the blood? The release of insulin into the bloodstream leads to a reduction in the levels of circulating glucose through a number of pathways. First, insulin activates the proteins that actively transport glucose from the blood into the interior of cells where is can be used as a source of energy. In addition, insulin also stimulates liver cells to convert glucose into glycogen.
What are the Islets of Langerhans?
These are small groups of cells that are found in the pancreas and which release various hormones directly into the blood. The islets of Langerhans only comprise about 1-2% of the total number of cells in the pancreas, the main function of this organ being to release digestive enzymes into the intestine. There are three types of cells in the islets of Langerhans, each synthesizing a different molecule that regulates the balance of energy metabolism in the body. ?-cells secrete glucagon, a polypeptide made of 29 amino acids, into the blood. Glucagon has the opposite effects to insulin, in that it causes glycogen to be broken down into glucose by the liver, and it stimulates adipose tissue to release fatty acids. ?-cells secrete insulin into the blood in response to high levels of glucose. ?-cells secrete a small peptide called somatostatin. This peptide inhibits insulin release and glucagon from the ? and ?-cells of the pancreas.
What is glycogen?
Glucose is stored in cells in the form of a complex polymer called glycogen. This molecule is very similar in structure to starch except that it has a large number of branches from each chain. When glucose is available in large amounts in muscle and adipose tissues, insulin release activates How does glucose enter cells? Glucose molecules cannot pass directly through cell membranes. Their entry is effected by the presence of proteins that create holes by spanning the membrane. These proteins are called glucose transporters, and five different forms have been characterized, each with slightly different properties and distribution throughout the tissues. For example, GLUT2 is found in the ?-cells of the pancreas and in liver cells. Insulin does not appear to affect the ability of GLUT2 to transport glucose. Muscle and fat cells, on the other hand, possess the GLUT4 transporter which is stimulated by insulin so that more glucose is taken up by these cells when blood insulin levels are high. Red blood cells contain large amounts of the GLUT1 glucose transporter, the structure of which appears to consist of twelve cylinders that pass through the membrane and which are arranged in a circle to create a pore.
What is the difference between Type 1 and Type 2 diabetes mellitus?
Type 1 diabetes often strikes suddenly in early childhood and results from the destruction of the ?-cells in the pancreas. These cells synthesize and secret insulin into the blood where it can exert its effects. Current evidence suggests that it takes several years for the immune system to attack the pancreatic ?-cells, and diabetes results when approximately 80% of them are destroyed. Type 2 diabetes mellitus usually occurs for reasons of diet in individuals with a genetic predisposition for this genetic condition. In this disease, the pancreas secretes normal levels of insulin into the blood, but there appears to be a lack of insulin receptors on liver cells. Hence, removal of glucose form the blood through glycogen synthesis does not take place. Equally, cells are not stimualte to transport glucose from the blood. The exact pathway of this regulation of insulin receptor levels seems unclear at present.
What is known about the insulin receptor?
For various reasons, it is believed that the insulin has an insulin-binding domain which is on the outside of a cell that is connected to a domain by a polypeptide segment that is bound within the cell membrane. In common with many other protein hormone receptors, the two molecules of the insulin receptor are brought together by one insulin molecule. When the receptor assumes a dimeric form, then the intracellular domain can act to catalyze the phosphorylation of various proteins in the cell, using the breakdown of ATP as an energy source. This event then leads to activation of the cell systems that allow glucose to be transported from the blood into the cell, where the sugar is either broken down to release energy or used to form glycogen, a polymer of glucose that acts as an energy store.
What is the structure of insulin?
Insulin is a very complex protein that is made from two polypeptide chains. It has been crystallized and so the three-dimensional structure is known at the molecular level. Unfortunately, insulin has a tendency to form complex structures involving six individual insulin molecules when it forms crystals. As single molecules of insulin are biologically active, it is hard to be sure of the structural form of insulin that binds to its receptor. However, by using techniques to engineer the amino acid sequence of proteins, a mutant form of insulin has been produced that does not form complex oligomeric structures when it crystallizes. Such information can be used as part of efforts to discover new molecules that can bind to the insulin receptor and act in a similar way to the protein hormone. Such compounds might be used as drugs in place of insulin, especially if they could be taken by mouth rather than by injection.
Why does the breath of an untreated diabetic smell of acetone (nail varnish remover)?
When fatty acids are broken down to form acetyl-CoA, a key compound in the generation of energy from oxygen, a side-reaction occurs in liver mitochondria that leads to the formation of acetoacetate. In turn, acetoacetate can undergo a variety of reactions. One of these involves the breakdown of acetoacetate to give carbon dioxide and acetone. Acetone cannot be used by the cell and therefore builds up in the blood. As acetone is relatively volatile, some of this compound is expelled from the lungs in the breath of the diabetic.