Hormonal communication 5.1.4
regulation of insulin levels
glucose regulation
Adrenal medulla
Adrenal cortex
Intro
testing for diabetes
Diabetes (diabetes mellitus)
how glucagon & insulin affects liver cells
They are regulating chemicals produced by endocrine glans
Characteristics of hormones...
1) Effective in small quantities
2) Usually small molecules
3) Often proteins / polypeptides or steroid
4) Transported in blood
5) Produced by endocrine system
6) Acts on target cells & tissues
Protein & peptide hormones (non-steroid hormones)
(e.g. insulin, glucagon, adrenaline)
Cannot get into the cell cause too big & insoluble in lipids
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1) They bind to receptors on the cell surface membrane forming a hormone receptor complex activating ‘G protein’
2) The 'G protein' activates an enzyme called adenylate cyclase
3) The activated adenylate cyclase converts ATP --> Cyclic AMP
4) Cyclic AMP acts as the 2nd messenger (1st messenger is the actual hormone molecule)
5) Cyclic AMP activates other enzymes within the cell to change what the cell does
Steroid hormones
(e.g. oestrogen, testosterone)
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1) They are soluble in lipids so pass across the phospholipid membrane
2) Once inside the cell they bind to a complimentary receptor protein (on cytoplasm, nuclear member need or in nucleus) that carries it to the nucleus
3) The hormone-receptor complex (acts as a transcription factor binds to a gene which it switch on & off thereby controlling the synthesis of a protein (e.g. enzyme)
The adrenal gland has an outer capsule surrounding 3 distinct layers of cells which are:
Capsule => adrenal cortex (3 layers) => adrenal medulla
Zona glomerulosa
Outer most layer of cortex
Secretes mineral corticoids
e.g. aldosterone
controls the sodium/potassium levels in the blood
controls blood pressure
acts on cells of DCT & collecting tube in kidney
Increases Na+ absorption & increases water retention, therefore increasing blood pressure
Zona fasciculata
Secretes Glucocorticoids
e.g. cortisol
Zona reticularis
Can also release cortisol but under right conditions can also release precursor androgens into the blood
These are taken up by ovaries & testes & converted into six hormones
Testosterone & oestrogen
These control development of secondary sexual characteristics & regulation of gamete production
Hormones from adrenal cortex
Cholesterol is used by adrenal cortex to make a range of hormones
They are steroid based/(steroid hormones) & can enter cell membranes directly by dissolving into them
How steroid hormones are made in adrenal Cortex affects their target cells
Released in response to stress or low glucose
Stimulates production of glucose in other sources
controls metabolism of carbs, fats, proteins in liver,
E.g. Glycogen, fats, proteins in liver
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Steroid hormone passes through cell membrane of target Ce
Binds to specific receptor (complementary shape) in cytoplasm
The receptor-steroid hormone complex enters the nucleus & binds to a specific receptor on the chromosomal material
The binding stimulates production of messenger RNA, which codes for the production of proteins
Adrenaline
polar molecule
Non-steroid hormone - can’t enter a cell membrane
must be detected by a receptor on plasma membrane of target cell
Role of adrenaline - Fight or flight:
Relaxes smooth muscle in bronchioles
Opens airways
Increased SV (stroke volume) of heart & heart rate
Increases volume of O2 delivered to muscles
General vasoconstriction
increases blood pressure
Conversion of glycogen to glucose
Dilates pupils
Increases mental awareness
Inhibition of gut action
Diverts blood from gut to muscles, not needed there at this stage
Body hair stand erect
The pancreas
Unusual cause its an endocrine (secrete hormones that flow directly into the blood) & exocrine (secretion they produce always flow down a duct) gland
Exocrine function:
exocrine cells are found in small groups surrounding tiny tubes
Each group is called a acinus
The tubules combine to make up the pancreatic duct which feeds into the duodenum
Contents of pancreatic juice (produced by acinus):
Pancreatic amylase
Pancreatic lipase
Trypsinogen (inactive precursor converted to trypsin when it reaches duodenum)
Sodium hydrogen carbonate (to neutralise acid from stomach)
Endocrine function:
Small patches of cells called eyelets of Langerhans
Contain Alpha & Beta cells
Alpha cells produce glucagon
Beta cells produce insulin
Insulin function – to bring about the fall of blood glucose conc, if blood glucose conc is too low its important insulin secretion stops
Normal glucose levels = 5mmol dm^-3
If too high (>10 mmol dm^-3) a condition called hyperglycaemia results
This has osmotic effects & can damage cells as water is drawn out of them
Glucose also appears in the urine & this is called glucosuria
High thirst
High urination
If blood glucose drops below 3mm dm^-3 then hypoglycaemia results
Not enough fuel in blood
Poor concentration
Cold sweats
Coma
So need to keep our blood glucose levels within narrow range 3 to 10
2 hormones help to regulate this
Insulin & Glucagon
Insulin
Peptide hormone (51 amino acids)
Secreted from Beta cells in eyelets of Langerhans in Pancreas
Secreted directly into blood stream to be circulated
What does it do:
Increases uptake of glucose by muscles & other tissues
Increases respiration of glucose by liver & other cells instead of using other substances e.g. fatty acids
Stimulates liver/muscle tissue to convert glucose to glycogen (glycogenesis). They enzyme which insulin activates to so this called glycogen synthetase
Inhibits the breakdown of lipids in the adipose tissue
Inhibits breakdown of glycogen (glycogenolysis)
All of these actions cause or help blood glucose levels to drop
Glucagon
29 amino acids
Produced by alpha cells in eyelet of Langerhans in pancreas
Antagonistic to insulin,
Se related when there’s a fall in glucose levels in blood
Also insulin levels need to be low for glucagon to be secreted
Affects liver cells
Increases breakdown of glycogen to glucose (gylcogenolysis)
Conversion of lipids & amino acids to glucose (gluconeogesis)
Activates the enzyme glycogen phosphorylase - breaks down glycogen into glycogen
Deactivates glycogen synthetase
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Cell membrane has calcium & potassium ion channels
Potassium channels are open & potassium flows out
Glucose will diffuse in hen there is a high conc on the outside
Glucose is metabolised to produce ATP
This extra ATP causes potassium channels to close
Potassium ions no longer diffuse out & builds up in the cell
The change in potential different causes the voltage gated calcium channels to open
Calcium ion enter the Beta cell via diffusion & cause vesicles containing insulin ti migrate towards the cell surface membrane &. Secret insulin into the blood via exocytosis
Glucagon
1) Glucagon binds to receptors on the cell surface membrane of liver cell
2) G protein activated which activates Adenylate Cyclase
3) Adenylate Cyclase converts ATP to cyclicAMP [cAMP] (2nd messenger)
4) cAMP activates a series of enzyme controlled reactions inside the cell to change what it does…
Glycogen converted to glucose (glycogenolysis)
More fatty acids used in respiration
Amino acids/fats converted to glucose (gluconeogenesis)
5) The overall effect of all these pathways is to raise blood glucose level
Insulin
1) Target cell have specific receptors (liver cells in this case)
2) Insulin binds & activates the enzyme tyrosine kinase
3) Tyrosine kinase causes phosphorylation of inactive enzymes within the cell
4) Activating these enzymes causes a cascade of enzyme controlled reaction inside the cell
5) More transporter proteins specific to glucose are placed into the cell surface membrane - this is achieved by causing vesicles containing these transport proteins to fuse with the membrane
6) More glucose enters the cell
7) Glucose converted to glycogen
8) More glucose converted to fats
9) More glucose respired
Symptoms:
Glucose in urine
Thirst
Copious urine secretion
Weight loss
Fatigue
Acid Ketosis on blood due to fats broken dome - acidic blood
2 types of Diabetes Mellitus
Type I Diabetes - Insulin dependant diabetes / juvenile onset diabetes
- Early in life
Autoimmune response
Destruction of beta cells
Caused by genetics or virus
- Patient must be given insulin injections
Treating:
1) Insulin injection
2) Insulin pump - needle always in skin
Short needle to inject into fat for gradual release
3) Inlet cell transplant of beta cells from a healthy patient into the pancreas
4) Complete pancreas transplant
5) Stem cell from Bon marrow / placenta
Blood glucose levels:
Glucose is always higher in the diabetic
Much slower decrease
Doesn't return to base level
Mainly relying on kidneys to excrete excess glucose
Insulin levels
Diabetic doesn't produce enough insulin cause most beta cells have been destroyed
Type II Diabetes - non-insulin dependant diabetes / mature onset diabetes
- Occurs later in life
- Common in old people & obese people
- Due to high sugar diet & lack of exercise
- Asian / Afro-Caribbean origin
- Family history
- The response to sensitivity to insulin is reduced we see insulin resistance occurring cause of constant elevated level
- Type II can often be controlled with diet / exercise.
If we live to 100 we will all be type II diabetics eventually
Treating:
1) Change lifestyle
2) Lose weight
3) Exercise more
4) Monitor diet - match carb intake to use
5) Drugs which slow glucose absorption
Blood glucose levels:
Diabetic has higher blood glucose level
Much slower return to base line
Insulin levels:
Insulin is released in diabetic but cells aren't responding to it
Liver isn't removing glucose
So blood glucose remains higher
Sources of insulin
- Source of Human Insulin - genetically modified bacteria
- Exact copy to human insulin
Advantages:
Less chance of developing tolerance compared to animal insulin
Less chance of rejection
Lower risk of infection
Cheaper to make with genetically modified bacteria than extract from animals
More controllable / adaptable to demand (grown in fermenter) compared to rearing animals which takes years
Fewer objections (ethics) on using bacteria instead of animals
Chemical messages transported away from their site of manufacture to act on other parts (target cells/tissue)
They bind to receptors with complementary shapes
In animals they are produced by endocrine glands and travel in the blood
In plants they are produced by a variety of tissues and travel by active transport, diffusion and also in the xylem/phloem
Release of theses hormones controlled by hypothalamus & anterior pitutary gland
Key words
Gluconeogenesis = making new glucose from amino acids
Glycogenesis = making glycogen
Glycogenolysis = break down of glycogen