Control of Insulin Secretion

Control of Insulin Secretion

Formerly, it was believed that insulin secretion was controlled almost entirely by the blood glucose concentration. However, as more has been learned about the metabolic functions of insulin for protein and fat metabolism, it has become apparent that blood amino acids and other factors also play important roles in controlling insulin secretion (see Table 78–1).

Increased Blood Glucose Stimulates Insulin Secretion. Atthe normal fasting level of blood glucose of 80 to 90 mg/100 ml, the rate of insulin secretion is minimal— on the order of 25 ng/min/kg of body weight, a level that has only slight physiologic activity. If the blood glucose concentration is suddenly increased to a level two to three times normal and kept at this high level thereafter, insulin secretion increases markedly in two stages, as shown by the changes in plasma insulin concentration seen in Figure 78–8.

1. Plasma insulin concentration increases almost 10-fold within 3 to 5 minutes after the acute elevation of the blood glucose; this results from immediate dumping of preformed insulin from the beta cells of the islets of Langerhans. However, the initial high rate of secretion is not maintained; instead, the insulin concentration decreases about halfway back toward normal in another 5 to 10 minutes.

2. Beginning at about 15 minutes, insulin secretion rises a second time and reaches a new plateau in 2 to 3 hours, this time usually at a rate of secretion even greater than that in the initial phase. This secretion results both from additional release of preformed insulin and from activation of the enzyme system that synthesizes and releases new insulin from the cells.

Feedback Relation Between Blood Glucose Concentration and Insulin Secretion Rate. As the concentration of bloodglucose rises above 100 mg/100 ml of blood, the rate of insulin secretion rises rapidly, reaching a peak some 10 to 25 times the basal level at blood glucose con-centrations between 400 and 600 mg/100 ml, as shown

in Figure 78–9. Thus, the increase in insulin secretion under a glucose stimulus is dramatic both in its rapid-ity and in the tremendous level of secretion achieved. Furthermore, the turn-off of insulin secretion is almost equally as rapid, occurring within 3 to 5 minutes after reduction in blood glucose concentration back to the fasting level.

This response of insulin secretion to an elevated blood glucose concentration provides an extremely important feedback mechanism for regulating blood glucose concentration. That is, any rise in blood glucose increases insulin secretion, and the insulin in turn increases transport of glucose into liver, muscle, and other cells, thereby reducing the blood glucose concentration back toward the normal value.