6.1 Insulin

The normal level of glucose in blood is between 80-90 mg/100ml or 4-6 mMolar. When the level of glucose goes up (after eating a meal), the beta (ß) cells of the pancreas secrete insulin. When the level of glucose begins to fall, the alpha cells of the pancreas secrete glucagon which acts mostly on the liver to liberate glucose from stored glycogen. Thus, the effects of the two hormones counterbalance each other.

Figure 43. Relationships between insulin and glucagon action

For insulin to act, it must bind to insulin receptors . These receptors are membrane proteins found on many tissues (see diagram). The action of insulin is complex and changes with time.

Figure 44. The binding of insulin to its receptor leads to complex intercellular reactions.

Short term effects

Within seconds after insulin binds to a receptor complex, the receptor proteins become phosphorylated and a receptor tyrosine kinase is activated which may lead to other cellular proteins becoming phosphorylated.

Within minutes there is a large increase in transport of glucose due to a large migration of glucose transporter proteins from the interior of fat and muscle cells to the cell membrane. Liver always has a very large capacity to take up glucose. The excess glucose is converted into glycogen for storage. A change in gene regulation occurs, leading to turning on of new genes. Some insulin receptor in taken into the cell.

Longer term effects

There is an increase in glycogen synthesis in liver, fat synthesis increases in fat cells, and growth-promoting factors are synthesized (insulin-like growth factor). As glucose levels fall in blood, insulin secretion also declines. Soon glucagon is released which stimulates glycogen breakdown in liver with release of glucose into the circulation and activation of a hormone-sensitive lipase in fat cells which stimulates release of fatty acids to be used as alternate energy sources to glucose.

Glucose Flux

Humans use about 10 gm/hr of glucose when resting and 40 gm/hr during exercise. After a meal, about 30 gm/hr may pour into the blood stream. This glucose must be rapidly removed by the liver and muscle and stored as glycogen.

Figure 45. Glucose flux in the resting state (A) and after eating (B). There are rapid increases in glucose transporters in muscle (squares) and fat cells (squares) in respond to insulin action.