The Endocrine Pancreas 2 Flashcards
What class of hormone is glucagon?
Peptide hormone
What is the primary function of glucagon?
Raise blood glucose, it is a glucose mobilising hormone that mainly acts on the liver
What is the plasma half life of glucagon?
5-10 minutes
Where is glucagon mainly degraded?
In the liver
What system does glucagon form part of, which opposes the actions of insulin?
Glucose counter-regulatory control system
What does the glucose counter regulatory control system consist of?
Glucagon
Epinephrine
Cortisol
Growth hormone
Is glucagon most active in the absorptive or post-absorptive state?
Post-absorptive state
What kind of receptors are glucagon receptors?
G-protein coupled receptors linked with adenylate cyclase/cAMO system
What does the activation of glucagon receptors cause?
Increased glycogenolysis
Increased gluconeogenesis
Formation of ketones from fatty acids (lipolysis)
What effect does increased blood glucose have on insulin and glucagon?
Increased insulin secretion
Decreased glucagon secretion
Decreased blood glucose has the opposite effects
How do amino acids impact the release of insulin and glucagon?
Stimulates the release of both, which is an adaptation to adjust for the composition of a meal very high in protein
If not for this effect on glucagon then the insulin stimulating effects would result in very low [BG]
What is meant by obligatory glucose user?
Endocrine system ensures there is enough glucose circulating to supply the needs of the brain
Other than the brain, what can tissues use when glucose is not available?
Free fatty acids and ketones to produce energy
What are examples of stimuli that promotes glucagon release?
- Low [BG] (<5mM)
- High [amino acid]
- Prevents hypoglycaemia following insulin response to amino acids
- Sympathetic innervation and epinephrine, b2 effect
- Cortisol
- Stress
- Such as exercise, infection
What are examples of stimuli that inhibits glucagon release?
- Glucose
- Free fatty acids (FFA) and ketones
- Insulin
- Fails in diabetes so glucagon levels rise despite high [BG]
- Somatostatin
How does parasympathetic activity (vagus nerve) impact Islet cells?
Increases insulin and to a lesser extent increases glucagon, in association with the anticipatory phase of digestion
How does sympathetic activity impact Islet cells?
Promote glucose mobilisation, so increased glucagon, increased epiniphrine and inhibition of insulin, all appropriate for fight or flight response
Give a summar of glucose counter regulatory controls for:
muscle glycogenolysis
liver glycogenolysis
gluconeogenesis
inhibition of glucose uptake
lipolysis
protein catabolism
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What class of hormone is somatostain?
Peptide hormone
What is somatostatin produced by?
D cells of the pancreas
Hypothalamus
What is somatostatin also known as?
Growth hormone inhibiting hormone (GHIH)
Wjhat is the main action of somatostatin?
To inhibit activity in GI tract, slow down absorption of nutrients to prevent exaggerated peaks in plasma concentration
What can synthetic somatostatin (SS) be used for clinically?
To help patients with life-threatening diarrhoea associated with gut or pancreatic tumours
What effect does somatostain have on insulin and glucose?
It is not a counter regulatory hormone in the control of blood glucose
But it does strongly suppress the release of both insulin and glucagon in a paracrine fashion
What effect does somatostain have on growth hormone?
Inhibits its release from anterior pituitary
What can disruption of the steady state be caused by?
Exercise
Starvatopm
Diabetes
How does exercise affect the entry of glucose into skeletal muscle?
Entry of glucose into skeletal muscle is increased during exercise, even in the absence of insulin
How does exercise impact the insulin sensitivity of a muscle?
Increases it and causes an intulin-independent increase in the number of GLUT-4 transporters incorporated into muscle membrane
What is the difference in migration of GLUT-4 transporters during exercise and when not exercising?
When not exercising, requires insulin to activate
When exercising, can migrate to membrane without insulin being present
How does the body get energy during starvation?
When nutrients are scarce the body relies on stores for energy, adipose tissue is broken down and fatty acids are released
FFA can be used by most tissues to produce energy and liver will convert excess to ketone bodies which provide additional source of energy for brain and muscles
Why does the brain adapt after a period of starvation to use ketones?
To save proteins that would otherwise be broken down to provide gluconeogenic substrates
Can be brain always use ketones as fuel?
No, it needs to adapt to be able to use them - which it does after a period of starvation
Why are proteins of the body the last store to be depleted in starvation?
It is very weakening and leaves you vulnerable to infection
What are the 2 main forms of diabetes?
Type 1
Type 2
What is type 1 diabetes also known as?
Insulin dependent diabetes mellitus (IDDM)
What does IDDM stand for?
Insulin dependent diabetes mellitus
What is type 1 diabetes?
Autoimmune destruction of pancreatic B cells meaning loss of ability to produce insulin and compromises ability to absorb glucose from plasma
What percentage of diabetic patients have type 1 diabetes?
10%
Why do type 1 diabetics take daily injections and not an oral tablet?
Peptide hormones cannot be given orally
What would happen to a type 1 diabetic who did not take insulin injections?
Excessively wasted, develop keoacidosis, coma and die
What is a consequence of the body thinking it is starving in diabetes?
Liver produces glucose which makes the problem worse
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Why does ketoacidosis occur in diabetes?
Normally, when nutrients are scarce the body relies on stores for energy (adipose tissue broken down and free fatty acids release)
However, in poorly controlled insulin dependent diabetes a lack of insulin depresses ketone body uptake so they build up rapidly in the plasma and because they are acidic create life threatening acidosis (ketoacidosis or ketosis) with plasma pH < 7.1
What are indicators of ketoacidosis?
Ketones are detectable in urine and produce distinctive acetone smell to breath
What is type 2 diabetes also called?
Non-insulin dependent diabetes mellitus (NIDDM)
What does NIDDM stand for?
Non-insulin dependent diabetes mellitus
What happens in type 2 diabetes?
Peripheral tissues become insensitive to insulin (called insulin resistance)
Muscle and fat can no longer respond to normal levels of insulin, either due to abnormal response of insulin receptors or a reduction in their number
B cells remain intact (may even be insulinaemia)
What percentage of diabetics are type 2?
90%
What is type 2 diabetes typically associated with?
Obesity and usually appears >40 years but age is decreasing
What is the treatment for type 2 diabetes?
1) Initial tretment is aimed at trying to restore insulin sensitivity of tissues with exercise and dietary changes
2) If this fails, oral hypoglycaemic drugs will be used
3) Eventually end up taking insulin
What is a glucose tolerance test?
Patient ingests glucose load after fasting [BG] measured
[BG] will normally return to fasting levels within an hour, elevatin after 2 hours is indicative of diabetes
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Can a glucose tolerance test distinguish type 1 from type 2 diabetes?
No, it cannot
What are examples of diabetic complications?
Retinopathy
Neuropathy
Nephropathy
Cardiovascular disease
What are complications of hypoglycaemia in diabetes?
Cognitive dysfunction
Lethargy
Coma
Convulsions
Permanent brain damage and death
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