Cells need a stable environment to survive. Homeostasis is the mechanism that allows living organisms to maintain relatively constant levels of temperature, pH, ions and water balance. These mechanisms are controlled by processes known as negative feedback, in which the system responds to environmental changes by releasing molecules, such as hormones, to exert an effect on the body that will reverse a high or low trend and restore levels to within the normal range.
Blood glucose homeostasis
Cells derive their energy from glucose, and it is vital that glucose levels be tightly regulated. Too much glucose is toxic to cells while too little glucose leads to starvation. Blood glucose levels can fluctuate for a number of reasons, such as digestion after a meal and production of insulin by the liver, both of which lead to increased glucose levels, or from the transport of sugar into the cells and the loss of glucose in the urine, which lower blood glucose levels. Glucose homeostasis relies on many different molecules, cell types and organs.
Central Role of Hormones: Insulin and Glucagon
Glucose concentrations in the blood stream are primarily controlled by the action of two antagonistic pancreatic hormones, insulin and glucagon. Glucose is first detected in the bloodstream by glucose transporter receptors expressed on the surface of specialized pancreatic cells known as alpha- and beta-cells. Beta-cells respond to rising levels of blood glucose by secreting the hormone insulin. Insulin restores normal levels of glucose in the blood by signaling body tissues to take up glucose for energy, or to convert glucose to glycogen and lipids as future energy stored in the liver, muscle and fat cells. In the event of low levels of glucose, the alpha-cells of the pancreas release the hormone glucagon to stimulate skeletal muscle and the liver to breakdown glycogen into glucose and adipose tissue to digest lipids into fatty acids and glycerol. Glucagon also stimulates the liver to synthesize glucose from glycerol in the blood. All these reactions work together to raise glucose levels back to normal.
The Impact of Diabetes
According to the American Diabetes Association, an estimated 23.6 million children and adults in the United States have diabetes; of these, 5.7 million are not aware that they have the disease and another 57 million people have pre-diabetes. In 2007, the total economic cost of the disease was estimated to be $174 billion, with medical expenditures accounting for $116 billion of the total. These figures are expected to rise dramatically if current trends in obesity, diabetes and other chronic conditions continue.
Type 1 Diabetes
Type 1 diabetes is an autoimmune disease in which the body's immune system malfunctions and attacks and destroys the beta-cells in the pancreas. This renders the pancreas unable to synthesize insulin and therefore cells can not be signaled to take up glucose, and blood glucose levels remain high. Type 1 diabetics require an external source of insulin to regulate glucose.
Type 2 Diabetes
The most common form of diabetes is Type 2. The high numbers of adolescents now developing this disorder is of particular concern to health experts. In this disease, the tissues in the body become resistant to insulin over time and are unable to respond to insulin signals. For a while, the body is able to compensate for the emerging resistance by increasing insulin production, but eventually the pancreas fails to produce enough insulin to meet the body's demand, due in part to the mass depletion of beta-cells. High blood glucose levels result because cells no longer take up glucose and the liver is unable to slow either its conversion of glycogen into glucose or its synthesis of glucose from glycerol.
Alzheimer's Disease and the "Type 3 diabetes" hypothesis
Diabetes is a recognized risk factor for the development of Alzheimer's disease. While it is not proven, increasing evidence has led a number of experts to believe that the pathology of Alzheimer's disease in at least some patients may be caused by insulin resistance or low insulin in the brain, leading them to approach the disease as "diabetes of the brain" or "Type 3 diabetes." The Alzheimer's Association reports that as many as 5.3 million people in the United States are living with Alzheimer's and that the direct and indirect costs of Alzheimer's and other dementias to Medicare, Medicaid and businesses comes to more than $148 billion each year. With the aging U.S. population, these costs are expected to skyrocket in the future.