1. © SSER Ltd.

2. Compare the action of the endocrine system with the nervous system:
Hormone action
Compare the action of the endocrine system with the nervous system:
Similarities
Differences
Both use chemical messengers (although in different ways)
Both involved in maintaining a constant internal environment
Both respond to changes in external conditions
Hormonal control is slower acting
Effects are (mostly) longer lasting for hormonal control
Hormones may have more than one target tissue whereas neurones only activate one effector.

3. Blood Glucose Regulation
Glucose is the most common respiratory substrate utilised by cells, and is the sole energy source for the brain and red blood cells
In normal circumstances,
blood glucose levels remain remarkably stable as they are
under the homeostatic control of two pancreatic hormones – insulin and glucagon
In 1923, Banting and Macleod were awarded the Noble Prize for the discovery and isolation of the hormone insulin, a breakthrough that was to have a profound effect on the lives of sufferers of diabetes

4. Many body tissues can use fatty acids as a source of metabolic energy in addition to, or instead of, glucose
In contrast, the brain and red blood cells require glucose as their sole energy source; brain disturbance rapidly occurs if this nervous tissue is deprived of glucose
Red blood cells lack mitochondria and can only obtain their energy by anaerobic glycolysis

5. Sources of Blood Glucose
The glucose that circulates in the bloodstream is derived from three main sources:
Dietary intake and digestion of carbohydrates
Glycogenolysis; the breakdown of stored glycogen into glucose
Gluconeogenesis; the conversion of non-carbohydrate sources, such as amino acids, into glucose

6. Dietary carbohydrates include sugars, starch
and cellulose; during digestion, disaccharide
sugars (e.g. maltose) and starch are hydrolysed
to yield glucose
The conversion of non-carbohydrates (e.g. amino acids and glycerol) into glucose by liver cells is called gluconeogenesis
Glycogenolysis is the conversion of glycogen (storage carbohydrate
found in liver and muscle tissue) into glucose; the released glucose enters
the bloodstream

7. Blood Glucose Regulation
Blood glucose levels are controlled by two principal hormones, insulin and glucagon, secreted by the endocrine portion of the pancreas, as well as adrenaline (from the adrenal glands).
The pancreas contains clusters of endocrine cells, called the Islets of Langerhans, which secrete the hormones insulin and glucagon into the bloodstream
The concentration of glucose in the blood normally lies in the range of 90 – 100 mg/100 cm3
A rise in blood glucose level to above the norm, for example after a meal, is detected by the beta cells of the Islets of Langerhans, which respond by secreting insulin
If the blood sugar level drops below the norm, for example between meals, or after fasting, then the alpha cells of the Islets of Langerhans detect this change and respond by secreting glucagon

8. Negative feedback mechanisms operate to achieve glucose homeostasis

9. Blood Glucose Regulation Insulin decreases levels of blood glucose by:
Increasing the permeability of body cells to glucose by stimulating the incorporation of additional glucose carriers into cell membranes and by opening additional transport channels
Increasing respiratory rate of cells – cells use up more glucose
Glycogenesis; activation of the liver enzymes that convert glucose into glycogen (also occurs in muscle cells)
Lipogenesis; stimulates the conversion of glucose into fatty acids in adipose tissue (fat cells)

10. Blood Glucose Regulation
Glucagon increases levels of blood glucose by:
Glycogenolysis; activation of the liver enzymes that convert glycogen into glucose
Gluconeogenesis; activation of the liver enzymes that convert non-carbohydrates e.g. amino acids and glycerol into glucose
Lipolysis; stimulates the breakdown of triglycerides into fatty acids and glycerol in adipose tissue
There are several other hormones that can increase blood glucose, the most well-known of these is adrenaline.

11. detected by the alpha cells detected by the beta cells
glucagon secretion
insulin secretion
Dual Hormonal Control achieves Glucose Homeostasis
Glycogen to glucose
non-carbohydrates to glucose
Glucose to glycogen
increased permeability of body cells to glucose
release of fatty acids from adipose tissue
uptake of glucose for fatty acid synthesis

12. beta cells of the Islets of Langerhans in the pancreas
detected by the
beta cells of the Islets of Langerhans in the pancreas
activation of enzymes that promote the conversion of glucose into glycogen in liver and muscle tissue
increase in the permeability of body cells to glucose
activation of enzymes that promote fat synthesis
insulin
secretion
rise in
blood glucose
restoration of the norm
(negative feedback)
restoration of the norm
(negative feedback)
fall in
blood glucose
activation of enzymes that promote the conversion of glycogen into glucose in liver tissue and fatty acid release in adipose tissue
activation of enzymes that promote the conversion of non-carbohydrates, such as amino acids, into glucose (gluconeogenesis)
glucagon
secretion
detected by the
alpha cells of the Islets of Langerhans in the pancreas

13. Effect of insulin on the glucose permeability of cells
Insulin binds to
receptors on cell
surface membranes
Effect of insulin on the glucose permeability of cells
glucose carrier for
facilitated diffusion
plasma
membrane
intracellular
chemical
signal
signal triggers the fusion of carrier-containing vesicles with the surface membrane
The additional carriers increase glucose permeability

14. The glucagon second messenger is a small molecule called
Hormone Action
Protein hormones, like insulin and glucagon, are polar, lipid-insoluble molecules that are unable to diffuse through the lipid bilayer of plasma membranes
These hormones bind to receptor proteins in the plasma membranes of their target cells, and trigger a chain of events that activate or inhibit the enzymes required for specific biochemical reactions
The hormone itself is the ‘first messenger’; on binding to a receptor at the surface of a target cell, the hormone activates specific molecules at the membrane that lead to the release of a ‘second messenger’, which enters the cytoplasm and triggers a response
The glucagon second messenger is a small molecule called
cyclic AMP; the involvement of two messengers – the hormone and cyclic AMP – amplifies the original signal; cyclic AMP is a widely studied second messenger molecule although other molecules perform this function for certain hormones

15. the inner surface of the membrane Hormone -induced change
Adrenaline, glucagon or insulin all work by the second messenger model. The hormone binds to a
surface receptor
Binding induces a change in the shape of the receptor, which activates an enzyme located on
the inner surface of the membrane
Hormone -induced change
Cyclic AMP
(second messenger)
cAMP activates enzymes required for specific biochemical reactions
inactive enzyme
active enzyme
Enzyme converts ATP into cyclic AMP
Activated enzymes produce specific changes in the cell

16. Hormone Action and Amplification triggered by the hormone
When a protein hormone binds to its cell-surface receptor, a CASCADE OF EVENTS is triggered with one event leading inevitably to another
Each molecule within the cascade system activates many molecules of the next stage, such that there is an AMPLIFICATION of the original message
triggered by the hormone
A single molecule of hormone promotes the synthesis of thousands of the molecules of the final product

17. G-protein Adenyl cyclase
Each activated receptor protein activates many molecules of adenyl cyclase
Each activated adenyl cyclase molecule converts many molecules of ATP into cyclic AMP
Each cyclic AMP molecule activates many copies of the desired enzyme
Each enzyme molecule catalyses the formation of many molecules of product
The binding of one hormone
molecule at the cell surface promotes the synthesis of thousands of cyclic AMP molecules (amplification); a small concentration of hormone in the blood produces a massive response within the target cell
G-protein
Adenyl cyclase

18. Glucose enters the bloodstream
Glucagon binds to
surface receptor
Many molecules of adenyl cyclase are activated, each of which converts many molecules of ATP into cyclic AMP
Glucose enters the bloodstream
Many molecules of Cyclic AMP
cAMP activates many copies of the enzyme that splits glycogen into glucose
inactive enzyme
active enzyme
A phosphorylase
enzyme catalyses the conversion of glycogen into glucose

20. Diabetes mellitus A breakdown in the homeostatic control of blood
glucose concentration may lead to a condition
called diabetes mellitus
Diabetes mellitus is characterised by an inability of cells to take up glucose from the blood which, in untreated cases, forces the cells to draw on other sources of energy, such as fat and protein reserves; blood glucose concentrations
exceed the renal threshold and glucose is excreted in the urine
Diabetes mellitus may arise when the pancreatic beta cells fail to produce insulin (or produce insufficient amounts), OR when
the insulin receptors at cell membranes become abnormal

21. There are two principal types of diabetes mellitus:
Type I or Juvenile-onset Diabetes appears suddenly during childhood as a result of the destruction of the insulin-producing cells of the pancreas; this is thought to arise from either a viral infection or an attack by the individual’s own antibodies (autoimmune reaction); sufferers of Type I diabetes are insulin-dependent
Type II or Maturity-onset Diabetes is generally a less severe form of the condition, in which insulin levels may be normal or reduced, but the target cells fail to respond to the hormone due to receptor abnormalities

22. The Glucose Tolerance Test
When an individual is suspected of having diabetes, a glucose tolerance test is usually performed
The test is used to determine the capacity of the body to tolerate ingested glucose
The glucose tolerance test involves the following steps:
Fasting for eight hours
A blood test to determine fasting, blood glucose concentration (time 0 minutes)
Ingestion of a glucose load (usually 50 grams)
Blood tests for monitoring blood glucose concentrations at regular intervals over a period of 2½ hours
Results are graphed to give a glucose tolerance curve

23. Present these results in graphical form
Time after ingesting glucose (mins)
Blood Glucose
Concentration (mmol/l)
normal
mild diabetes
severe diabetes
4.4
11.8 30
6.3
7.9
14.3 60
17.6 90
4.0
10.0
17.3
120
4.2
7.8
17.1
150
4.3
6.4
16.9
Present these results in graphical form

24. Describe and explain the differences between the three curves

25. Effects of Diabetes mellitus
Undersecretion of insulin, and the subsequent inability of cells to utilise glucose as a respiratory substrate, leads to a variety of metabolic effects in untreated diabetics - these include:
Hyperglycaemia; an increase in blood glucose concentration and the excretion of glucose by the kidneys
Protein Catabolism; the breakdown of muscle protein to amino acids in response to the inability to use glucose as a principal respiratory substrate; excess amino acids are converted into both glucose and urea in the liver, increasing the excretion of nitrogen and raising blood glucose levels (an unwanted effect)
Fat Catabolism; stored fats are hydrolysed to fatty acids and utilised by cells for respiration; excessive fatty acid oxidation produces an excess of acetyl CoA molecules that are converted to ketones by the liver; the release of ketones into the blood lowers the pH (acidosis)
Osmotic Diuresis; the high concentration of glucose in the urine creates a hypertonic urine that reduces water reabsorption from the collecting ducts; a large volume of urine is excreted

26. Stored fats are converted to fatty acids and used by body cells for respiration; large quantities of acetyl CoA are a by-product of fatty acid oxidation and these are converted to ketones in the liver; ketones make the blood acidic
Muscle protein is broken down into amino acids producing a surplus that is converted into
both urea and glucose in the liver; increased excretion of urea leads to a loss of nitrogen from the body

27. The high concentrations of glucose in the blood are such
that they exceed the renal threshold and are excreted in
the urine; this produces a hypertonic urine that enters
the collecting ducts of the
kidney tubules
The hypertonic urine reduces the water potential gradient between the urine and the hypertonic tissue of the kidney medulla
As the urine flows through the collecting ducts, less water is reabsorbed and a large volume of urine is produced (diuresis)
Large volume
of urine
This loss of water can lead to dehydration, and extreme thirst may be experienced

28. Treatment of Type I diabetes is by subcutaneous injection of insulin; insulin cannot be taken orally as the protein nature of this hormone would result in its digestion within the gut
The insulin dose needs to be adjusted carefully; an excessive dose of insulin together with a low carbohydrate intake results in hypoglycaemia (low blood sugar level)
Blood glucose levels are regularly monitored to determine the need for insulin; biosensors are used by individuals to keep track of their sugar levels

29. Treatment of Type II diabetes largely involves dietary control
Nutritionists work with sufferers to devise a healthy eating plan that limits sugar intake and is balanced by an appropriate level of exercise
Modern methods of treatment enable individuals, with either Type I or Type II diabetes, to
lead normal lives