Regulate insulin secretion
Stimulation of insulin secretion by amino acids is important because insulin, in turn, enhances the transport of amino acids to the cells, as well as the formation of proteins in the cells.
There were times when it was believed that insulin secretion was controlled almost entirely by blood glucose levels. However, as more is known about the metabolic function of insulin for protein and fat metabolism, it has become clear that blood amino acids and other factors also play an important role in the control of insulin secretion. insulin (see table).
Board. Factors and conditions that increase or decrease insulin secretion
Increased blood glucose stimulates insulin secretion
Normal fasting glucose concentration is about 80-90mg/100ml, low insulin secretion is about 25ng/min/kg, level with only mild physiological activity. If blood sugar spikes suddenly two to three times above normal and stay at this high level thereafter, insulin will increase secretion clearly in two stages.
Figure. The increase in plasma insulin concentration after a sudden increase in blood glucose is two to three times the normal level. Note an initial rapid rise in insulin levels followed by a delayed but higher and continued increase in concentrations beginning 15 to 20 minutes later.
1. The plasma concentration of insulin increases about 10-fold in the 3 to 5 minutes following a sudden rise in blood glucose. This is the result of an immediate release of insulin already present in the beta cells of the islets of Langerhans. However, this large level of secretion is not maintained, instead, the insulin concentration is reduced by about half in 5-10 minutes.
2. Starting after about 15 minutes, insulin secretion increases for a second time and reaches a new peak in 2 to 3 hours, during which time insulin secretion is usually greater than in the first phase. This result is due to the additional release of existing insulin and activation of the enzyme system that synthesizes and releases new insulin from the cell.
Feedback between blood glucose levels and insulin secretion
If glucose levels rise above 100mg/100ml, insulin secretion accelerates, peaking at 10-25 times baseline when blood glucose levels are around 400-600mg/100ml as shown in Figure 79-9. Therefore, increased insulin secretion in a glucose-stimulated state is impressive in terms of both the rate and extent of insulin secretion that can be achieved. Furthermore, the cessation of insulin secretion is equally rapid, occurring within 3 to 5 minutes after blood glucose levels fall to fasting levels.
Figure. Approximate insulin secretion at different plasma glucose levels
This response of insulin secretion to elevated blood glucose concentrations provides an extremely important feedback mechanism for blood glucose regulation. That is, hyperglycemia increases insulin secretion, and insulin, in turn, increases the rate of glucose transport into the liver, muscle, and other cells, leading to a decrease in blood glucose levels back to normal values.
Other factors that stimulate insulin secretion
Amino acids. Several amino acids have glucose-like effects in stimulating insulin secretion. The most powerful are arginine and lysine. This effect is different from that of glucose: Amino acids control the absence of hyperglycemia and cause only a very small increase in insulin secretion. However, when simultaneously high blood glucose is controlled, insulin secretion can be doubled in the presence of an excess of amino acids. Therefore, amino acids play a role in enhancing the insulin secretion of glucose.
Stimulation of insulin secretion by amino acids is important because insulin in turn enhances the transport of amino acids to the cells, as well as the formation of proteins in the cells. Therefore, insulin is as important for the proper utilization of excess amino acids as it is for carbohydrate utilization.
Gastrointestinal Hormones. A mixture of several important gastrointestinal hormones – gastrin, secretin, cholecystokinin, glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) – can induce moderate hyperinsulinemia. Two of these hormones, GLP-1 and GIP, are the most expressed and are often referred to as incretins because they increase the degree of insulin release from islet beta cells in response to increased plasma glucose. They also inhibit glucagon secretion from the alpha cells of the islets of Langerhan.
These hormones are released in the gastrointestinal system after eating. They then cause a "pre-effect" to increase insulin in the blood in preparation for the absorption of glucose and amino acids from food. These hormones often act in the same way as amino acids, increasing the sensitivity of insulin secretion to glucose in response to hyperglycemia, almost doubling the amount of insulin secreted while blood glucose levels rise. As will be discussed later in this chapter, many drugs have even been developed to mimic or enhance the effects of incretin for the treatment of diabetes.
Other hormones and the autonomic nervous system
Other hormones that either directly increase insulin secretion or increase glucose sensitivity to insulin secretion include glucagon, growth hormone, cortisol, and partly progesterone and estrogen. The importance of the stimulant effects of these hormones is that prolonged
secretion of any one of them in large quantities can sometimes lead to depletion of Langerhans beta cells and thereby increase the risk for the development of diabetes. Indeed, diabetes often occurs in people receiving high and sustained doses of some of these hormones. Diabetes is especially common in the rich or in people with acromegaly, who have growth hormone-secreting tumours, as well as in people whose adrenal glands secrete excess glucocorticoids.
Pancreatic islets are diverse in the distribution of sympathetic and parasympathetic nerves. Stimulation of parasympathetic nerves to the pancreas may increase insulin secretion in hyperglycemic conditions, whereas sympathetic stimulation may increase glucagon secretion and decrease insulin secretion in hypoglycemia. . Glucose levels are thought to be detected by specialized neurons of the hypothalamus and brain stem, as well as by sugar-sensing cells in peripheral regions such as the liver.