Mar 8, 2013

Insulin and Glucagon: Control of Blood Glucose

Although the pancreas is considered a major endocrine gland, hormone–secreting cells make up only 1–2% of its weight. The rest of the pancreas produces bicarbonate ions and digestive enzymes, which are released into small ducts and carried to the small intestine via the pancreatic duct. Tissues and glands that discharge secretions into ducts are described as exocrine. Thus, the pancreas is a dual endocrine and exocrine gland with important functions in both the endocrine and digestive systems.

Clusters of endocrine cells, the islets of Langerhans, are scattered throughout the exocrine tissue of the pancreas. Each islet has a population of alpha cells, which produce the hormone glucagon, and a population of beta cells, which produce the hormone insulin. Both of these protein hormones, like all endocrine signals, are secreted into the circulatory system.


This is a critical bioenergetic and homeostatic function, because glucose is a major fuel for cellular respiration and a key source of carbon skeletons for the synthesis of other organic compounds. Metabolic balance depends on maintaining blood glucose concentrations near a set point, which is about 90 mg/100 mL in humans. When blood glucose exceeds this level, insulin is released, and its effects lower blood glucose concentration. When blood glucose drops below the set point, glucagon is released, and its effects increase blood glucose concentration. Each hormone operates in a simple endocrine pathway that is regulated by negative feedback. The combination of the two pathways permits precise regulation of blood glucose.

Target Tissues for Insulin and Glucagon
Insulin lowers blood glucose levels by stimulating virtually all body cells except those of the brain to take up glucose from the blood. (Brain cells are unusual in being able to take up glucose without insulin; as a result, the brain has access to circulating fuel almost all the time.) Insulin also decreases blood glucose by slowing glycogen breakdown in the liver and inhibiting the conversion of amino acids and glycerol (from fats) to glucose.

The liver, skeletal muscles, and adipose tissues store large amounts of fuel and are especially important in bioenergetics. The liver and muscles store sugar as glycogen, whereas adipose tissue cells convert sugars to fats. The liver is a key fuel–processing center because only liver cells are sensitive to glucagon. Normally, glucagon starts having an effect before blood glucose levels even drop below the set point. In fact, as soon as excess glucose is cleared from the blood, glucagon signals the liver cells to increase glycogen hydrolysis, convert amino acids and glycerol to glucose, and start slowly releasing glucose back into the circulation.
The antagonistic effects of glucagon and insulin are vital to glucose homeostasis and thus to the precise management of both fuel storage and fuel consumption by body cells. The liver′s ability to perform its vital roles in glucose homeostasis results from the metabolic versatility of its cells and its access to absorbed nutrients via the hepatic portal vessel, which carries blood directly from the small intestine to the liver.

Diabetes Mellitus
When the mechanisms of glucose homeostasis go awry, there are serious consequences. Diabetes mellitus, perhaps the best–known endocrine disorder, is caused by a deficiency of insulin or a decreased response to insulin in target tissues. There are two major types of diabetes mellitus with very different causes, but each is marked by high blood glucose.
In people with diabetes, elevated blood glucose exceeds the reabsorption capacity of the kidneys, causing them to excrete glucose. This explains why the presence of sugar in urine is one test for diabetes. As glucose is concentrated in the urine, more water is excreted along with it, resulting in excessive volumes of urine and persistent thirst. (Diabetes, from the Greek diabainein, to pass through, refers to this copious urination; and mellitus, from the Greek meli, honey, refers to the presence of sugar in urine.) Without sufficient glucose available to meet the needs of most body cells, fat becomes the main substrate for cellular respiration. In severe cases, acidic metabolites formed during fat breakdown accumulate in the blood, threatening life by lowering blood pH.

Type I diabetes mellitus (insulin–dependent diabetes) is an autoimmune disorder in which the immune system destroys the beta cells of the pancreas. Type I diabetes, which usually appears during childhood, destroys the person′s ability to produce insulin. Treatment consists of insulin injections, usually several times daily. In the past, insulin for injections was extracted from animal pancreases, but now human insulin can be obtained from genetically engineered bacteria, a relatively inexpensive source.

Type II diabetes mellitus (non–insulin–dependent diabetes) is characterized either by a deficiency of insulin or, more commonly, by reduced responsiveness of target cells due to some change in insulin receptors. Although heredity can play a role in type II diabetes, research indicates that excess body weight and lack of exercise significantly increase the risk. This form of diabetes generally appears after age 40, but young people who are overweight and sedentary can also develop the disease. More than 90% of people with diabetes have type II. Many can manage their blood glucose level with regular exercise and a healthy diet; some require drug therapy.