Question

NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

(Preparation Assignment for "Living the Sweet Life" by Breanna N. Harris)

4. Describe how insulin (a) is produced (b) is stored (c) is released (d) alters uptake of glucose, and (d) is broken down in the body.

5. What is a glucose tolerance test? Why/when is this test conducted? What are normal results for this test?

6. What is a dexamethasone suppression test? Why is it used clinically?

Answer 1

4. ANS: Insulin is secreted by beta cells of the pancreas. The secretion of insulin from pancreatic beta cells is a complex process involving the integration and interaction of multiple external and internal stimuli. Thus, nutrients, hormones, neurotransmitters, and drugs all activate or inhibit insulin release. The primary stimulus for insulin secretion is the beta-cell response to changes in ambient glucose.

Insulin is a protein/peptide based hormone that is synthesized and stored in beta cells of Islets of Langerhans in pancreas. This hormone increases the absorption of glucose into muscles and fat tissues and helps in regulation of carbohydrate and fat metabolism. It is released in response to an increased level of glucose in the blood and thus, is a classic example of humoral stimuli.

When the blood glucose levels are too high then B cells in the ilets of the langerhans, in the pancreas will secrete insulin. Insulin cell can promote absorption of glucose. Muscles are hepatocytes that convert glucose into glycogen. In adipose tissue the insulin promotes glycogen synthesis and reduces high level glucose which present in the blood. When the blood glucose levels are too low then a cells in the ilets of the langerhans, in the pancreas will secrete hormone glucagon. The high glucose levels of blood are antagonistically regulated by insulin and glucagon. If the insulin levels are low or absent, then the glucose concentration in the plasma exceeds and the uncontrolled glucose concentration leads to many diseases.

Normally, glucose induces a biphasic pattern of insulin release. First phase insulin release occurs within the first few minutes after exposure to an elevated glucose level; this is followed by a more enduring second phase of insulin release. Of particular importance is the observation that first-phase insulin secretion is lost in patients with type 2 diabetes. Thus, molecular mechanisms involved in basic insulin secretion are important

A widely accepted sequence of events involved in glucose-induced insulin secretion is as follows:

1. Glucose is transported into beta cells through facilitated diffusion of GLUT2 glucose transporters.

2. Intracellular glucose is metabolized to ATP.

3. Elevation in the ATP/ADP ratio induces closure of cell-surface ATP-sensitive K+ (KATP) channels, leading to cell membrane depolarization.

4. Cell-surface voltage-dependent Ca2+ channels (VDCC) are opened, facilitating extracellular Ca2+ influx into the beta cell.

5. A rise in free cytosolic Ca2+ triggers the exocytosis of insulin.

Insulin stimulates glucose transport in peripheral tissue (Skeletal muscles): The muscles do use large amounts of glucose. One of these is during moderate or heavy exercise. This usage of glucose does not require large amounts of insulin because exercising muscle fibers become more permeable to glucose even in the absence of insulin because of the contraction process itself. Muscle usage of large amounts of glucose is during the few hours after a meal. At this time the blood glucose concentration is high and the pancreas is secreting large quantities of insulin. The extra insulin causes rapid transport of glucose into the muscle cells. This causes the muscle cell during this period to use glucose preferentially over fatty acids.

IDE (Insulin degrading enzyme) or Insulin protease or insulysin cleave the enzyme insulin into multiple short polypeptides and later the amino acids present in the insulin can degrade sequently.

5. ANS: Glucose tolerance test (GTT): In the glucose tolerance test, the patient is asked to drink a standard amount of glucose solution within five minutes. The timing starts alter the drink is finished. Then the phlebotomist collects the blood samples periodically. That is at the 1st hour, at the 2nd hour, and so on. The total number of draws is determined by the physician. The patients have to fast and take adequate fluid during the test process so they can remain hydrated. Generally a normal glucose tolerance test result can indicates blood sugar that is equal to or less than 140 mg/dL (7.8 mmol/L) 1 hour after drinking the glucose solution.

6. ANS: Dexamethasone suppression test generally measures that ACTH secreted by pituitary can be suppressed. This is basically a synthetic dose of glucocorticoid after that the level of cortisol can be determined from blood. There are generally two different types of test for Dexamethasone suppression test that is low dose and high dose. This consists of an overnight and standard 3 days process.

Low dose overnight: 1 milligram dose of dexamethasone is given in night and next morning blood is drawn at 8:00 am to measure the level of cortisol and this results in decreasing the the cortisol level to about 50 nanomoles per litre.

High dose overnight: The level of cortisol measured in the morning and after that 8mg dose of dexamethasone is provided at 11:00 pm and next morning at 8:00 am the level of cortisol is measured and this results in decrease of 50 percent reduction in plasma cortisol.

This test is performed basically when body is producing too much cortisol. It is done to help to diagnose the cushing syndrome. so that low dose is given when ACTH produces cortisol in excess and high dose is given in case of Cushing syndrome which causes problem in pituitary gland.

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