Question

Part II. ADDITIONAL QUESTIONS 1.) Where in the body is insulin made? Where is glucagon made? 2.) a) What is the effect of insulin on glucose uptake in muscle? b) How about in liver? c) How about in adipose tissue? d) How about in brain? 3.) a) What would you expect with regards to fasting glucose levels in a patient that had a pancreatic tumor characterized by rapid proliferation and uncontrolled growth of b-cells? b) How about a pancreatic tumor characterized by rapid proliferation and uncontrolled growth of a-cells? 4.) If a glucose tolerance test were performed on an animal that had been treated several days before with alloxan, what results would you expect? Why? 5.) Insulin is generally administered via either intramuscular or subcutaneous (just under the skin) injections. Do you see any potential problems that might be associated with administering insulin in oral tablet form? If so, briefly discuss them. (Hint: insulin is a protein).

Answer 1

1. The hormone insulin is a main regulator of the glucose (sugar) levels in the blood.Insulin is produced in the pancreas. To be more specific, it's produced by the beta cells in the islets of Langerhans in the pancreas. When we eat, glucose levels rise, and insulin is released into the bloodstream.

Glucagon is a hormone that is involved in controlling blood sugar (glucose) levels. It is secreted into the bloodstream by the alpha cells, found in the islets of langerhans, in the pancreas.

2. Insulin facilitates entry of glucose into muscle, adipose and several other tissues. The only mechanism by which cells can take up glucose is by facilitated diffusion through a family of hexose transporters. In many tissues - muscle being a prime example - the major transporter used for uptake of glucose (called GLUT4) is made available in the plasma membrane through the action of insulin.When insulin concentrations are low, GLUT4 glucose transporters are present in cytoplasmic vesicles, where they are useless for transporting glucose. Binding of insulin to receptors on such cells leads rapidly to fusion of those vesicles with the plasma membrane and insertion of the glucose transporters, thereby giving the cell an ability to efficiently take up glucose. When blood levels of insulin decrease and insulin receptors are no longer occupied, the glucose transporters are recycled back into the cytoplasm.

Insulin stimulates the liver to store glucose in the form of glycogen. A large fraction of glucose absorbed from the small intestine is immediately taken up by hepatocytes, which convert it into the storage polymer glycogen.Insulin has several effects in liver which stimulate glycogen synthesis. First, it activates the enzyme hexokinase, which phosphorylates glucose, trapping it within the cell. Coincidently, insulin acts to inhibit the activity of glucose-6-phosphatase. Insulin also activates several of the enzymes that are directly involved in glycogen synthesis, including phosphofructokinase and glycogen synthase. The net effect is clear: when the supply of glucose is abundant, insulin "tells" the liver to bank as much of it as possible for use later.

A well-known effect of insulin is to decrease the concentration of glucose in blood, which should make sense considering the mechanisms described above. Another important consideration is that, as blood glucose concentrations fall, insulin secretion ceases. In the absense of insulin, a bulk of the cells in the body become unable to take up glucose, and begin a switch to using alternative fuels like fatty acids for energy. Neurons, however, require a constant supply of glucose, which in the short term, is provided from glycogen reserves.When insulin levels in blood fall, glycogen synthesis in the liver diminishes and enzymes responsible for breakdown of glycogen become active. Glycogen breakdown is stimulated not only by the absense of insulin but by the presence of glucagon, which is secreted when blood glucose levels fall below the normal range.

We haven’t developed a type of oral insulin that can make it through the digestive system unharmed. The acids in your stomach break down oral insulin before it can get to your liver. That means it’s not effective by the time it reaches your liver.Further, your body has trouble absorbing insulin from your intestines. The mucus layer in your intestines is thick, and studies have shown that only low levels of insulin pass through this lining and into your bloodstream. As a result, some researchers believe that high doses of insulin would be needed to be effective in managing diabetes.Many clinical trials have been done on oral insulin, but no form of the treatment has made it through the trials successfully. The good news is, none of these trials has shown major health risks from oral insulin as compared to injectable insulin.However, researchers are concerned that oral insulin could raise the risk of certain types of cancer. This is because large amounts of insulin would be needed to make it through the digestive system. Insulin is a growth-promoting substance, and large amounts of it could promote the growth of cancer cells. The bottom line, though, is that there's no established link between oral insulin and cancer.