The insulin signalling pathway

A significant stress faced by all animals is the unpredictable cycle of feeding and then starvation that ensues between meals. Humans solve this problem by storing nutrients in forms that can be used as energy sources during periods of fasting. The driving force that regulates this process is insulin, a hormone released by the β-pancreatic islet cells in response to elevated levels of nutrients, such as glucose in the blood supply. Insulin binds to its receptor on the major insulin responsive tissues of the body namely skeletal muscle, adipose tissue and liver. This triggers the activation of a signalling pathway whose function is first to stimulate the transport of nutrients, such as glucose, amino acids and fatty acids, from the blood supply to these tissues and, secondly, to promote the conversion of these nutrients into storage macromolecules, such as glycogen, protein, and lipids. Failure to regulate the uptake and storage of nutrients efficiently following feeding results in diabetes, which is estimated to affect ~2% of the world population. Type 1 diabetes is characterised by the failure to synthesise insulin and affects ~10% of diabetics; it normally occurs in childhood and can be treated with daily injections of insulin. In contrast, type 2 diabetes affects ~90% of diabetics and usually occurs in adults. In this form of diabetes the target tissues become resistant to the effects of insulin, presumably because the insulin-signalling pathway is impaired. Type 2 diabetes can only be moderately controlled by regimes of poorly effective drugs and nutritional control. Patients suffering from this form of diabetes invariably suffer long-term complications including kidney and heart disease, loss of sight, and their life expectancy is reduced on average by 5–10 years.