Insulin is a protein hormone produced by the beta cells of the pancreas, which enables the body to metabolise and use glucose. It has a major affect on the metabolism of carbohydrates and lipids, and a significant but lesser effect on protein metabolism.
Insulin enters a cell by mean of an insulin receptor, which is found within the plasma membrane. The insulin receptor is comprised of two alpha sub-units and two beta sub-units, which are linked by a disulfide bond. Insulin receptors are tyrosine-kinase receptors, meaning that their function is to transfer phosphate groups from ATP to intracellular proteins, which increase glucose transporter molecules on the outer membrane of cells, which facilitate an uptake of glucose.
Carbohydrates
Carbohydrates are broken down to monosaccharides in the small intestine, and absorbed from the small intestine to the hepatic portal vein. A rise in the concentration of glucose stimulates the release of insulin, which acts on cells throughout the body to stimulate the uptake, and storage of glucose. Insulin's effect on glucose metabolism varies according to the tissue destination. Insulin aids the entry of glucose into muscle, adipose and other tissue by facilitated diffusion using a glucose transporter (GLUT). For example muscle use a transporter called GLUT4. Insulin regulates glucose uptake by moving intracellular vesicles containing the GLUT4 glucose transporters to the cell surface, where glucoses enter s by facilitated diffusion. However not all tissue require insulin for uptake of glucose, the brain and liver use a different sort of non-insulin dependant transporter.
Insulin also stimulates the liver to store glucose in the form of glycogen. If glucose absorbed from the small intestine is not immediately required for ATP energy, it is taken up by the hepatocytes, which convert glucose into glycogen. Insulin activates the enzyme hexokinase, which phosphorylates glucose causing it to remain in the cell. Insulin also activates enzymes such as glycogen synthase, which is responsible for glycogen synthesis.
Fat
Insulin stimulates hepatocytes to synthesize fatty acids once glycogen stores are full. Fatty acids are taken from the liver as lipoproteins and broken down by lipase. The fatty acids are either utilized straight away or stored as triglycerides in adipose tissue. . Insulin facilitates entry of glucose into fat cell, to be synthesized as glycerol, (fatty acids plus glycerol combine to form triglycerides). When the body's store of glycogen is used, triglycerides are broken down by lipase into their component parts. Hormones such as glucagon, adrenaline and growth hormone activate lipase; these hormones are active when insulin is not present. The resulting glycerol and fatty acids are released into the blood, and travel to the liver through the bloodstream.
Protein
If insulin is present, proteins are digested, broken down into amino acids and used to synthesise the body's protein requirements. If amino acids are in excess of immediate requirements they are either used for ATP, or converted to fat for later use. In the absence of insulin (either due to lack of food or conditions such as diabetes) the body's supply of glycogen is quickly used. In order to supply the body with glucose alpha cells in the pancreas secrete glucagon, which acts on the same cells as insulin, but has the opposing effect. It stimulates the liver and muscles to release stored glycogen - glycogenolysis. Other hormones capable of stimulating glycogenolysis are cortisol, thyroxine, adrenaline and growth hormone. These hormones also stimulates glucose from non-carbohydrate sources - gluconeogenesis from either glycerol, lactate from glycolysis of red blood cells, but mainly from stored amino acids in muscle tissue. Insulin levels then rise to respond to and increased level of blood glucose.
Diabetes and Insulin Resistance
Lack of insulin (type 1 diabetes) or insulin resistance (type ll diabetes) cause high blood glucose. After a meal, even though blood glucose levels are high, cellular uptake cannot be facilitated. The body reacts by initiating glycogenolysis and gluconeogenesis, which further raise blood glucose. High levels of glucose causes frequent urination as glucose in the kidney filtrate draws in water due to osmosis. Constant urination increases thirst, by increasing osmotic pressure of the blood, which directly stimulates thirst receptors. Increase in urination also increases the loss of sodium, which also stimulates thirst receptors. Glycogenolysis and gluconeogenesis lead to fat loss and muscle loss, which lead to weight loss. Metabolism of fatty acids may produce ketone bodies, which can lead to breathing problems; a lowered blood PH decreased nerve firing and possibly coma and death. Therefore it is necessary to control diabetes by either medication to act as insulin, (type 1 diabetes) or by dietary and lifestyle measures (type ll). Thus it can be concluded that the function of insulin has a fundamental effect on metabolism.
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