cortisol's stimulation of the superoxide dismutase, since this copper enzyme is almost certainly used by the body to permit superoxides to poison bacteria. Other effects Metabolism Glucose Cortisol counteracts insulin, contributes to hyperglycemia by stimulating gluconeogenesis and inhibits the peripheral use of glucose (insulin resistance) by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane. Cortisol also increases glycogen synthesis (glycogenesis) in the liver, storing glucose in easily accessible form. The permissive effect of cortisol on insulin action in liver glycogenesis is observed in hepatocyte culture in the laboratory, although the mechanism for this is unknown. Bone and collagen Cortisol reduces bone formation, favoring long-term development of osteoporosis (progressive bone disease). The mechanism behind this is two-fold: cortisol stimulates the production of RANKL by osteoblasts which stimulates, through binding to RANK receptors, the activity of osteoclasts – cells responsible for calcium resorption from bone – and also inhibits the production of osteoprotegerin (OPG) which acts as a decoy receptor and captures some RANKL before it can activate the osteoclasts through RANK. In other words, when RANKL binds to OPG, no response occurs as opposed to the binding to RANK which leads to the activation of osteoclasts. It transports potassium out of cells in exchange for an equal number of sodium ions (see above). This can trigger the hyperkalemia of metabolic shock from surgery. Cortisol also reduces calcium absorption in the intestine. Cortisol down-regulates the synthesis of collagen. Amino acid Cortisol raises the free amino acids in the serum by inhibiting collagen formation, decreasing amino acid uptake by muscle, and inhibiting protein synthesis. Cortisol (as opticortinol) may inversely inhibit IgA precursor cells in the intestines of calves. Cortisol also inhibits IgA in serum, as it does IgM; however, it is not shown to inhibit IgE. Electrolyte balance Cortisol decreases glomerular filtration rate, and renal plasma flow from the kidneys thus increasing phosphate excretion, as well as increasing sodium and water retention and potassium excretion by acting on mineralocorticoid receptors. It also increases sodium and water absorption and potassium excretion in the intestines. Sodium Cortisol promotes sodium absorption through the small intestine of mammals. Sodium depletion, however, does not affect cortisol levels so cortisol cannot be used to regulate serum sodium. Cortisol's original purpose may have been sodium transport. This hypothesis is supported by the fact that freshwater fish use cortisol to stimulate sodium inward, while saltwater fish have