Insulin - Counter regulatory hormone Flashcards
What is the key role of insulin in controlling blood glucose levels
1, high glucose levels – removal of glucose from the blood (transport)
- Synthesis of glycogen and triglycerides to store energy
- Inhibition of processes that release glucose/fatty acids
What is the main hormone that is used in fasting to control blood glucose levels
Glucaogn
describe what metabolism is like during fasting
- Low glucose levels –No glucose transport
- Glycogen and triglycerides are not synthesised anymore
- Processes that release glucose/fatty acids are not inhibited anymore
describe the structure of glucagon
- 29 amino acids
- one chain only
what islets of langhernas produce glucagon
alpha
describe how synthesis of glucagon takes place
- Frist synthesised as a preproglucagon
- Broken down into a proglucagon
- This is then broken down into a glucagon
name another hormone that comes from the same precursor as glucagon
GLP-1
how low is blood glucose in order to do glucagon secretion
- Stimulated by low blood glucose concentration – normal fasting levels of glucose is 80-90mg/100ml
what causes an increase in glucagon secretion
- Exercise - In exhaustive exercise blood concentration of glucagon increases four to five fold
(increased circulating amino acids or β-adrenergic stimulation may play a role)
what inhibits glucagon secretion
- inulin - it breaks down cAMP by phosphodiesterase enzyme
- somatostatin (produced by delta cells in the islet of langerhans)
what are the effects of glucagon
Increases glycogenolysis in the liver.
Increased uptake of amino acids in the liver.
Increases gluconeogenesis in the liver (amino acids, glycerol and lactate).
Liver glycolysis is inhibited by inhibiting pyruvate kinase and PFK1.
Increased lipolysis, glucagon activates hormone sensitive lipase (HSL).
More ketogenesis is able to occur.
how is glucagon receptor signalled
- The glucagon receptor is a G protein coupled receptor
- GPCRs contain 7 transmembrane domains are coupled to trimeric G proteins
- Dissociation of the trimer upon ligand binding to the receptor activates the signalling cascade
- In the absence of glucose, it is assembled in the trimeric form and the 3 subunits are joined together
- This activates adenylase cyclase and this activates cAMP
- The cAMP which is produced in this reaction triggers the cascade
- cAMP is produced and this activates PKA and then this increases phosphorylase kinase and activates the rest of the cascade causing glycogenolysis
what is CPT1
Important enzyme in the Beta oxidation of fatty acids into Acetyl-CoA.
what inhibits CPT1 and what activates CPT1
CPT1 is inhibited by insulin.
It is activated by glucagon.
what happens in prolonged glucagon
Oxaloacetate replaces amino acids as the main source for gluconeogenesis.
Acetyl-CoA is converted into acetoacetate (ketone) via HMG-CoA.
Glucagon inhibits HMG-CoA to prevent excess cholesterol and TGA formation.
But, glucagon increases ketogenesis.
what does triglycerides break down into
glycerol and free fatty acids
- glycerol is used in gluconeogensis
what does amlonyl CoA inhibit
- Malonyl-CoA inhibits transport of FFAs into mitochondria via CPT-1 therefore inhibiting β oxidation
what is oxaloacate used int he liver by
- oxaloacetate is used by the liver as substrate for gluconeogensis
what is excess acetyl-CoA converted into
- ketone bodies by the liver - keotgnesis
what is ketogensis inhibited by
- inhibited by insulin and activated by glucagon
name 3 catecholamines
- noradrenaline
- adrenaline
- dopamine
these are short term hormones
where is adrenaline released from
Released from the medulla of the adrenal glands.
what does adrenaline do
- Inhibits insulin secretion
- Stimulates glycogenolysis.
- Stimulates glucagon secretion.
- Increases lipolysis.
what is adrenaline and dopamine synthesis from
- Monoamines are synthesised from phenylalanine and tyrosine
when is adrenaline released
Released during stress or hypoglycaemia, also part of fight or flight response.
where are glucortoiciods produced
produced in the cortex
name an example of glucoroctoids
cortisol
some steroids
what causes the secretion of cortisol
ACTH released in the anterior pituitary gland causes secretion of cortisol.
is cortisol long term or short term
Long term = causes rapid utilisation of proteins and lipids.
what are the actions of cortisol
- It enhances gluconeogenesis
- It inhibits glucose uptake (and utilisation)
- It stimulates muscle proteolysis
- It stimulates adipose-tissue lipolysis
what can cortisol also help
Cortisol is important in resisting stress and inflammation
Cortisol helps maintain blood pressure and it suppresses inflammation
what can high cortisol levels cause
- Cushings sydrome
If levels of cortisol are elevated for a prolonged time they can induce proteolysis and muscle wasting
cortisol usually does not….
Cortisol usually does not mobilise basic functional proteins such as muscle contractile proteins and proteins of neurons
what do growth hormones do in
- adipose tissue
- liver
- skeletal muscles
Adipose Tissue:
Increases lipolysis.
Reduces glucose uptake.
Reduces lipogenesis.
Skeletal Muscle:
Reduces glucose uptake.
Increases lipoprotein lipase activity.
Liver:
Increases VLDL secretion.
Increases production and uptake of HDL and LDLs.
What do thyroid hormones do
T3 and T4 increase the activity and number of mitochondria, increasing the rate of
ATP synthesis.
Increase stimulation of carbohydrate metabolism:
- Rapid glucose uptake.
- Enhances glycolysis and gluconeogenesis.
- Increase insulin secretion.
Increase stimulation of fat metabolism:
- Lipids mobilised rapidly from adipose tissue.
- Fatty acid concentration in blood increased.
Overall effect is to increase basal metabolic rate.
what is more potent T3 or T4
- T3 is about 4 times more potent than T4
- T3 is present in the blood in much smaller quantities and persists for a much shorter time
what are incretins
- these are a group of gastrointestinal hormones
name some examples of incretins
Glucagon-like peptide-1 (GLP-1)
Gastric inhibitory peptide
what does GLP-1 do
- inhibits glucagon secretion and hepatic glucose production
- slows gastric emptying
- promotes satiety
- augments glucose-induced inulin secretion
- rests beta cell function
- increases insulin biosynthesis
- promotes B cell differentiation
what is hypoglycaemia
any abnormally low plasma glucose concentration
that exposes the subject to potential harm” with a proposed threshold
plasma glucose value <70 mg/dL (<3.9 mmol/L)
what cause cause hypoglycaemia
- can be caused by stimulation of glucose utilisation and inhibition of glucose release
High insulin doses
Alcohol excess (inhibition of gluconeogenesis)
Insulinoma (A tumour of pancreatic β cells)
Excessive exercise (Leading to increased glucose utilisation)
Reactive hypoglycaemia (Excessive insulin secretion in response to a high carbohydrate meal in the pre-diabetic condition)
what is a major combination of type I diabetes
- hypoglycaemia is a major combination of type I diabetes
what are the symptoms of hypoglycaemia
Autonomic symptoms
- Include trembling palpation, sweating, anxiety, hunger, tingling
Neuroglycopenic symptom s
- Including difficulty concentration, confusion, weakness, drowsiness, vision changes, difficulty speaking, dizziness, tiredness
Severe
- Confusion
- Disorientation
- Confusions
- Fitting
- Seizures
- Loss of consciousness
- Coma
what is prolonged hypoglycaemia caused
- Growth hormone and cortisol are secreted – they decrease the rate of glucose utilisation by most cells converting to fat utilisation
what are the consequences of hypoglycaemia
- Serious consequences related to neuroglycopaenia (shortage of glucose for the brain)
- Prolonged and repeated hypoglycaemia may produce permanent brain damage
- Loss of cognitive function, seizures and coma
how many type 1 diabetes patients get reccurnet severe hypoglycaemia
Recurrent severe hypoglycaemia affects 1-3% of Type 1 diabetes patients, mostly adults having diabetes for > 10 years
