You may have heard people make comments about their metabolism, for example ‘I am fat because I have a slow metabolism’. Your metabolism refers to all the things that are going on in your body to keep you alive. Different people have different metabolic rates. Some people have low metabolic rates and some have high metabolic rates. Metabolic rate may play a part in someone's weight but it is not usually the whole cause of being fat or thin. Glucose metabolism refers to the way in which glucose is processed in the body.
Fatty acids are released from fat and can be broken down in cells to produce energy. Ketone bodies, or ketones, are some of the products made when fatty acids are metabolised or processed.
Until the mid-1990s it was thought that fat tissue had little function other than as a fuel store. Although fat tissue is indeed a very important fuel source, it is now known that fat tissue also has many hormone-producing functions. Fat tissue is an important store for fat, which can be converted into fatty acids (Figure 4).
Question: What are the other glucose stores?
Glycogen in the liver and muscles.
Insulin stimulates glucose uptake into fat cells as well as into liver and muscle cells. A lack of insulin promotes the release of fatty acids from fat into the blood. As already mentioned the body tries to keep the glucose level tightly controlled. Overnight when one is fasting, fatty acids are released and can be used as a fuel. The way fat is broken down from fat stores is complex. Often the body breaks down fat and carbohydrate stores from the liver or muscles together. Fatty acids are produced which enter the metabolic pathways of the body and are used as fuel, and ketones are not formed. If fatty acids are broken down when little carbohydrate is available, they cannot be used normally as a fuel. Ketones are then produced from the fatty acids, and these ketones can be used as a fuel, as happens overnight when fasting, or in diabetes. If a person does not eat for a long time, then the body adapts to use the ketones as a fuel source, but excessive ketone production may be poisonous.
Insulin is very important in determining whether or not ketones are made. After eating, the insulin level is high which encourages glucose uptake into cells and hence suppresses ketone production. When fasting, the lower level of insulin allows ketones to form, but there is usually enough insulin to stop a build up of ketones. In people with diabetes who do not have insulin, the levels of ketones can build up. When the levels become too high the blood becomes acidic, a condition called ketoacidosis, and the person can become seriously ill.
Ketones can be detected in the urine (ketonuria) of a person after a prolonged fast, due to fat breakdown in the absence of carbohydrate. In people without diabetes ketonuria is not important and just means they have not eaten for a long time. In people with diabetes the presence of ketones in the urine can mean that they do not have enough insulin and that they are becoming unwell. Detection of ketones is an important part of helping people to manage their diabetes, especially if they are unwell.
The relationship between glucose, liver, skeletal muscle and fat is illustrated in Figure 4.
Glucose can pass easily between the blood and the liver and back again. This is shown by the two-way arrow in Figure 4. Glucose can also pass easily into the skeletal muscle and fat tissues, but in these cases glucose does not pass back into the blood. In skeletal muscle glucose is converted into glycogen and glucose released from glycogen is used to fuel muscle contraction. Fat tissue converts glucose into fatty acids and thence to fat, and when fat is broken down in normal metabolism fatty acids are produced again, and may be released back to the blood, and taken up by the liver. Here they are metabolised for energy and if insufficient carbohydrate is present ketones may be produced.
Case study 3 illustrates what can happen when someone with diabetes becomes unwell with an infection.
Case study 3
Miss Williams has had diabetes, that has been treated with insulin, for 50 years. She is now aged 80 and lives in a nursing home. Last winter she had a bad chest infection that stopped her from eating. Although she knew the important rule about never stopping her insulin she was too unwell to notice that her carers had not injected her insulin for her. Her carers thought that as she was not eating much, she would not need it. Very quickly Miss Williams became seriously ill. Although she had not eaten for 24 hours, by the time she was admitted to hospital her glucose level was 64 mmol/l (dangerously high), there were large quantities of ketones in her urine, and her blood, when tested at the hospital, contained more acid than it should. She had developed ketoacidosis because she had missed her insulin and sufficient glucose could not enter the cells and be used as a fuel.
With intravenous fluids and insulin Miss Williams made a good recovery.