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Blood Glucose RegulationGlucose 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
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
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
Dietary carbohydrates include sugars, starch and cellulose; during
digestion, disaccharide sugars (e.g. maltose)
and starch are hydrolysed
to yield glucose
Glycogenolysis is the conversion of glycogen (storage carbohydrate
found in liver and muscle tissue) into glucose; the released glucose enters
the bloodstream
The conversion of non-carbohydrates (e.g.
amino acids and glycerol) into glucose by liver cells is called gluconeogenesis
Blood Glucose Regulation
Blood glucose levels are controlled by two principal hormones, insulin and glucagon, secreted by the
endocrine portion of the pancreas
The pancreas is predominantly an exocrine gland (secreting many digestive enzymes into the gut); the
pancreas also 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 ( 5 – 5.6 mmol/l)
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
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
• 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)
A diabetic person and a non diabetic person ate the same
amount of glucose. One hour later, the glucose concentration in the blood of the diabetic person was higher than that of the non diabetic person. Explain why
3 marks
answer
• In a diabetic person:• Lack of insulin produced/reduce sensitivity
of cells to insulin because lack of receptors.• Reduced uptake of glucose by
body/liver/muscles cells• Reduced conversion of glucose to glycogen
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 into glucose
• Lipolysis; stimulates the breakdown of triglycerides into fatty acids and glycerol in adipose tissue
glucose glycogenglycogen glucosenon-carbohydrates glucose
detected by the alpha cells
detected by the beta cells
glucagon secretion insulin secretion
release of fatty acids from
adipose tissue
uptake of glucose for fatty acid synthesis
increased permeability of
body cells to glucose
Dual Hormonal Control achieves
Glucose Homeostasis
detected by the beta cells of the
Islets of Langerhans in the pancreas
rise inblood glucose
fall inblood glucose
detected by the alpha cells of the
Islets of Langerhans in the pancreas
restoration of the norm(negative feedback)
• 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)
restoration of the norm(negative feedback)
• 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
insulinsecretion
glucagonsecretion
Effect of insulin on the glucose permeability of cells
Insulin binds toreceptors on cell
surface membranes
intracellularchemical
signal signal triggers the fusion of carrier-
containing vesicles with the surface
membrane
The additional carriers increase
glucose permeability
glucose carrier forfacilitated diffusion
plasmamembrane
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
Hormone binds tosurface receptor
Binding induces a change in the shape of the receptor, which
activates a G-protein located on the inner surface of the membrane
The G-protein activates the enzyme
adenyl cyclase
Adenyl cyclase converts ATP
into cyclic AMP
Cyclic AMP(second messenger)
cAMP activates enzymes required for specific biochemical reactions
inactive enzyme active enzymeActivated enzymes
produce specific changes in the cell
Hormone -induced change
Hormone Action and Amplification
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
G-protein Adenyl cyclase
Each activated receptor protein activates many
molecules of adenyl cyclaseEach 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
Glucagon binds tosurface receptor
Many molecules of adenyl cyclase are activated, each of which converts many molecules of ATP into cyclic AMP
Many molecules of Cyclic AMP
cAMP activates many copies of the enzyme that splits glycogen into glucose
inactive enzyme active enzymeA phosphorylase
enzyme catalyses the conversion of
glycogen into glucose
Glucose enters the bloodstream
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
Diabetes mellitusThere 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
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 bodyto 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
Time after ingesting glucose (mins)
Blood Glucose Concentration (mmol/l)
normalmild
diabetessevere
diabetes
0 4.4 4.4 11.8
30 6.3 7.9 14.3
60 4.4 11.8 17.6
90 4.0 10.0 17.3
120 4.2 7.8 17.1
150 4.3 6.4 16.9Present these results in graphical form
Effects of Diabetes mellitusUndersecretion 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
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
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
If the glomerular filtrate of a diabetic person contains a high
concentration of glucose, he produces a larger volume of
urine. Explain why?
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)
This loss of water can lead to dehydration, and extreme thirst
may be experienced
Large volumeof urine
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 witha low carbohydrate intakeresults 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
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
A test for glucose in urine uses immobilised enzymes on a plastic test strip. One of these enzymes is glucose oxidase. Explain why the test strip detect glucose and
no other substance. 2 marks