Endocrine Control of Metabolism
Suggested Reading: Guyton Chapters 78
Glycogenesis (glycogen synthesis):
Diabetes (Type 1 and Type 2):
1. Discuss which metabolic pathways predominate during the fed and fasted state. Both insulin and glucagon function as important feedback control systems for maintaining a normal blood glucose concentration. When the glucose concentration rises too high, insulin is secreted; the insulin in turn causes the blood glucose concentration to decrease toward normal. Conversely, a decrease in blood glucose stimulates glucagon secretion; the glucagon then functions in the opposite direction to increase the glucose up toward normal. Under normal conditions the insulin feedback mechanism is many times as important as the glucagon mechanism, but in instances of starvation or excessive utilization of glucose during exercise and other stressful situations, the glucagon mechanism also becomes valuable.
2. Describe the factors that regulate the release of insulin and glucagon. As the concentration of blood glucose rises above 100 mg/dl, the rate of insulin secretion rises rapidly reaching a peak some 10-25 times the basal level at blood glucose concentrations. The increase in insulin secretion under a glucose stimulus is dramatic both in its rapidity and in the tremendous level of secretion achieved. The turn off of insulin secretion is almost equally as rapid occurring in 3-5 minutes after reduction in blood glucose concentration back to the fasting level. Amino acids administered in the absence of a rise in blood glucose cause only a small increase in insulin secretion but 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 excess amino acids. A mixture of several GI hormones cause a moderate increase in insulin secretion. They generally act the same way as amino acids to increase the sensitivity of insulin response to increased blood glucose. Glucagon, growth hormone, cortisol and to a lesser extent, progesterone and estrogen, either directly increase insulin secretion or potentiate the glucose stimulus for insulin secretion. The blood glucose concentration is the most potent factor in controlling glucagon secretion - it is the opposite direction from the effect of glucose on insulin secretion. Also, high concentrations of amino acids as occur in the blood after a protein meal, stimulate the secretion of glucagon. In exhaustive exercise, the blood concentration of glucagon often increases fourfold to fivefold. Somatostatin acts locally within the islets of Langerhans to depress the secretion of both insulin and glucagon - inhibits the secretion of them.
3. Describe the effects of insulin and glucagon as they relate to glucose metabolism. During the few hours after a meal, when the blood glucose concentration is high, the pancreas is secreting large quantities of insulin. The extra insulin causes rapid transport of glucose into the muscle cells. If the muscles are not exercising after a meal and yet glucose is stored in the form of muscle cells in abundance, then most of the glucose is stored in the form of muscle glycogen which can later be used for energy by the muscle. One of the most important effects of insulin is to cause most of the glucose absorbed afer a meal to be stored almost immediately in the liver in the form of glycogen. Then, between meals, when blood glucose concentration begins to fall, insulin secretion decreases rapidly and the liver glycogen is split back into glucose which is released back in the blood to prevent the concentration from falling too low. Glucagon is able to cause glycogenolysis in the liver which in turn increases the blood glucose concentration. Glucagon activates adenylcyclase which causes formation of cyclic adenosine monophosphate which activates protein kinase regulator protein, which activates protein kinase, which activates phophorylase b kinase which converts it to phophorylase a which promotes the degradation of glycogen into glucose-1-phosphate which is then phosphorylated and glucose is released from the liver cells. Even after all the glycogen in the liver has been exhausted under the influence of glucagon, hyperglycemia continues due to continued infusion of glucagon, resulting from the effect of glucagon to increase the rate of amino acid uptake by the liver cells and conversion of many of them to glucose by gluconeogenesis.
4. Define diabetes and differentiate between Type 1 and Type 2: Diabetes is a group of metabolic diseases characterized by hyperglcemia resulting from defects in either insulin secretion, action, or both.
Type I diabetes usually begins during childhood, but can occur at any age. Symptoms include polyuria, polydipsia, and weight loss. There is an osmotic pull of water into the urine to compensate from the increased amount of glc. It usually occurs abruptly due to some type of autoimmune response (possibly a viral agent, toxin, or random immunologic event). These individual release little or no insulin and need an outside source, which they are usually sensitive to. Without insulin during a prolonged fasting period, they can develop hyperglycemia or ketoacidosis. They do not respond to changes in diet alone or sulfonylurea or metformin.
Type II diabetes usually starts in adulthood, but has been more recently seen in children and adolescents. It has a gradual onset, and the main precipitating factor is obesity. Other factors include nutrition and age. Usually there is mild to none symptoms, and many are diagnosed during other exams or screenings. They have high insulin levels because their tissues do not respond to it. During prolonged fasting their glc levels will return to normal. They can get responses to changes in diet, exercise, and to drugs like sulgonylurea and metformin.
5. Discuss the general role of the catecholamines, cortisol and growth hormone in preventing hypoglycemia:
Return To The MNA 2001 Homepage