Medical brain notes 44

  Insulin and Its Metabolic Effects Insulin was first isolated from the pancreas in 1922 by Banting and Best, and almost overnight the outlook for the severely diabetic patient changed from one of rapid decline and death to that of a nearly normal person. Historically, insulin has been associated with “blood sugar,” and true enough, insulin has profound effects on carbohydrate metabolism. Yet it is abnormalities of fat metabolism, causing such conditions as acidosis and arteriosclerosis, that are the usual causes of death in diabetic patients. Also, in patients with prolonged diabetes, dimin-ished ability to synthesize proteins leads to wasting of the tissues as well as many cellular functional disorders. Therefore, it is clear that insulin affects fat and protein metabolism almost as much as it does carbohydrate metabolism. Insulin Is a Hormone Associated with Energy Abundance As we discuss insulin in the next few pages, it will become apparent that insulin secretion is associated...

  Effect of Insulin on Carbohydrate Metabolism Immediately after a high-carbohydrate meal, the glucose that is absorbed into the blood causes rapid secretion of insulin, which is discussed in detail later. The insulin in turn causes rapid uptake, storage, and use of glucose by almost all tissues of the body, but especially by the muscles, adipose tissue, and liver. Insulin Promotes Muscle Glucose Uptake and Metabolism During much of the day, muscle tissue depends not on glucose for its energy but on fatty acids. The principal reason for this is that the normal  resting muscle  mem-brane is only slightly permeable to glucose, except when the muscle fiber is stimulated by insulin; between meals, the amount of insulin that is secreted is too small to promote significant amounts of glucose entry into the muscle cells. However, under two conditions the muscles do use large amounts of glucose. One of these is during mod-erate or heavy exercise. This usage of glucose does not re...

  Effect of Insulin on Fat Metabolism Although not quite as visible as the acute effects of insulin on carbohydrate metabolism, insulin’s effects on fat metabolism are, in the long run, equally important. Especially dramatic is the long-term effect of  insulin lack  in causing extreme atherosclerosis, oftenleading to heart attacks, cerebral strokes, and other vascular accidents. But first, let us discuss the acute effects of insulin on fat metabolism. Insulin Promotes Fat Synthesis and Storage Insulin has several effects that lead to fat storage in adipose tissue. First, insulin increases the utilization of glucose by most of the body’s tissues, which automatically decreases the utilization of fat, thus functioning as a fat sparer. However, insulin also promotes fatty acid synthesis. This is especially true when more carbohydrates are ingested than can be used for immediate energy, thus providing the sub-strate for fat synthesis. Almost all this synthesis occurs in the li...

  Effect of Insulin on Protein Metabolism and on Growth Insulin Promotes Protein Synthesis and Storage.  During thefew hours after a meal when excess quantities of nutri-ents are available in the circulating blood, not only car-bohydrates and fats but proteins as well are stored in the tissues; insulin is required for this to occur. The manner in which insulin causes protein storage is not as well understood as the mechanisms for both glucose and fat storage. Some of the facts follow. 1.   Insulin stimulates transport of many of the amino acids into the cells . Among the amino acids moststrongly transported are  valine , leucine ,  isoleucine ,  tyrosine , and  phenylalanine . Thus, insulin shareswith growth hormone the capability of increasing the uptake of amino acids into cells. However, the amino acids affected are not necessarily the same ones.   2.   Insulin increases the translation of messenger RNA , thus forming new proteins. In some...

  Mechanisms of Insulin Secretion Figure 78–7 shows the basic cellular mechanisms for insulin secretion by the pancreatic beta cells in response to increased blood glucose concentration, the primary controller of insulin secretion. The beta cells have a large number of  glucose transporters (GLUT-2)  that permit a rate of glucose influx that is propor-tional to the blood concentration in the physiologic range. Once inside the cells, glucose is phosphorylated to glucose-6-phosphate by  glucokinase . This step appears to be the rate limiting for glucose metabolism in the beta cell and is considered the major mechanism for glucose sensing and adjustment of the amount of secreted insulin to the blood glucose levels. The glucose-6-phosphate is subsequently oxidized to form adenosine triphosphate (ATP), which inhibits the  ATP-sensitive potassium channels  of the cell. Closureof the potassium channels depolarizes the cell mem-brane, thereby opening  voltage-...

  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...

  Other Factors That Stimulate Insulin Secretion Amino Acids.  In addition to the stimulation of insulinsecretion by excess blood glucose, some of the amino acids have a similar effect. The most potent of these are  arginine  and  lysine.  This effect differs from glucose stim-ulation of insulin secretion in the following way: Amino acids administered in the absence of a rise in blood glucose cause only a small increase in insulin secretion. However, when administered at the same time that the blood glucose concentration is elevated, the glucose-induced secretion of insulin may be as much as doubled in the presence of the excess amino acids. Thus, the  amino acids strongly potentiate the glucose stimulus for insulin secretion. The stimulation of insulin secretion by amino acids is important, because the insulin in turn promotes transport of amino acids into the tissue cells as well as intracellular formation of protein. That is, insulin is important fo...