Endocrine pancreas and hormones (EAR 4)

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  • Created by: ftpptf
  • Created on: 19-04-19 16:07
Where is insulin synthesised?
Beta cells of islets of Langerhans of pancreas.
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What is the half life of insulin?
5-9 minutes.
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Why does insulin have such a short half life?
Released as a peptide hormone in the circulation (not bound to anything) so is susceptible to degradation by proteases.
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What does insulin gene transcription and translation initially produce?
Preproinsulin.
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What happens to preproinsulin in order to form proinsulin?
Cleavage of hydrophobic 'pro' signal along RER.
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What do we have at the end of the RER?
Proinsulin.
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Where is this proinsulin transported to?
Golgi.
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What happens to the proinsulin at the Golgi?
Further processing and cleavage to give insulin.
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What is cleaved from proinsulin to give insulin?
C-peptide.
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What enzymes are involved in the cleavage of the C-peptide?
Proconvertase 1 and 2. (PC1 cleaves at 32,33 and PC2 cleaves at 65,66).
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What enzyme then comes in to remove amino acids 31 and 32 and 64 and 65?
Carboxypeptidase H (CPH).
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What are amino acids 64 and 65 removed from by CPH?
C-peptide.
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What are amino acids 31 and 32 removed from by CPH?
B chain (gives mature insulin molecule).
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How many amino acids long is the previously 33aa C-peptide now?
31 amino acids.
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What is the ratio of insulin:C-peptide production from proinsulin.
1:1
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Where do these enzymes involved in the cleavage of proinsulin reside?
In the Golgi.
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Following cleavage of the C-peptide from proinsulin, what does the mature insulin molecule now do?
Precipitates out.
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What does insulin precipitate out with?
Zinc ions.
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What does this condensation of insulin with zinc ions form?
Dense crystalloid core within secretory granules.
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What is the ratio of zinc ions to insulin in the crystalloid core?
2 zinc ions : 6 insulin molecules.
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Where is insulin stored until it is required?
Secretory granules.
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What happens when insulin is needed?
Get movement of secretory granules towards plasma membrane. They fuse together and get release of insulin by exocytosis.
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What does this exocytosis involve?
Intracellular Ca2+ and energy in form of ATP.
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What is the main physiological regulator of insulin release?
Blood glucose (>5mM).
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How does a rise in blood glucose cause increased insulin release?
Rise in ATP:ADP ratio results in closure of ATP-sensitive K+ channels. This causes membrane depolarisation leading to the opening of voltage-gated Ca2+ channels.
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What other nutrient stimulus can stimulate insulin release?
Amino acids and fatty acids.
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What are incretins?
'Gut hormones'. Group of metabolic hormones that stimulate a decrease in blood glucose levels.
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When are incretins released?
When food is present in the gut.
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What do these incretins then do?
Potentiate insulin release. Body is anticipating the increase in blood glucose from the food you've just ingested.
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Give 2 examples of these gut hormones.
GLP-1 and GIP.
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What are GLP-1 and GIP secreted by respectively?
GLP-1 secreted by L cells in small intestine. GIP secreted by K cells in small intestine.
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What axis do these incretins potentiating insulin release in anticipation of food form part of?
Entero-insular axis.
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What else can potentiate insulin release?
Glucagon.
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Where is glucagon released from?
Islets cells.
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What is also released from the Islets cells but inhibits insulin release?
Somatostatin.
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What type of control does this represent?
Paracrine control.
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What else can influence insulin release?
Neural control.
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How does the sympathetic nervous system affect insulin release?
Activation of beta-adrenoceptors leads to increased insulin release. Activation of alpha2-adrenoceptors leads to decreased insulin release.
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How does the parasympathetic nervous system affect insulin release?
Activation of muscarinic receptors leads to increased insulin release.
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What are the actions of insulin?
Promote growth and development. Promote cellular uptake of K+ (via Na+K+ ATPase). Promote uptake and utilisation of glucose in skeletal muscle and adipose. Promote fuel storage (anabolic).
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How does insulin promote fuel storage?
Increases rate of synthesis and storage of energy reserves (glycogen and fats) and of protein.
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What effect does insulin action have on muscle cells?
Increase glucose uptake (via GLUT-4), increase protein synthesis and decrease protein breakdown.
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What effect does insulin action have on adipose tissue?
Increase glucose uptake (via GLUT-4), increase lipogenesis and decrease lipolysis.
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What effect does insulin action have on liver cells?
Increase glycogen synthesis, decrease glycogen breakdown and decrease gluconeogenesis.
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Therefore, what is the overall effect of insulin action?
Reduce blood glucose.
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What is insulin action mediated by?
Insulin receptor.
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What type of receptor are insulin receptors?
Tyrosine kinase.
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What type of hormone is glucagon?
Peptide hormone.
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Where is glucagon synthesised?
Alpha cells of Islets of Langerhans.
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What is the release of glucagon stimulated by?
Low blood glucose (<3.5mM), sympathetic and parasympathetic nervous systems and amino acids.
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What is glucagon release inhibited by?
High blood glucose, insulin and somatostatin.
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What is glucagon a counter-regulatory hormone to?
Insulin.
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What is the main action of glucagon?
Raise blood glucose.
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How does glucagon act to raise blood glucose?
Stimulate hepatic glycogenolysis. Stimulate hepatic gluconeogenesis. Stimulate lipolysis.
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What kind of interaction do glucagon and insulin have on plasma blood glucose levels?
Complementary.
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What type of hormone is somatostatin?
Peptide hormone.
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Where is somatostatin synthesised?
Delta cells off Islets of Langerhans. CNS (hypothalamus) and GI tract.
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What does somatostatin inhibit and by what mechanism?
Inhibits glucagon and insulin secretion by a paracrine mechanism.
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What is the normal range of glucose homeostasis?
4-8 mmol/L.
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What is glucose homeostasis a balance between?
Glucose production and glucose utilisation.
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What hormones act to increase glucose production when blood glucose gets too low?
Glucagon, adrenaline, growth hormone and cortisol.
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What are the most important regulators of normal fuel metabolism?
Insulin and glucagon (work as a team).
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In what state does adrenaline come in to act on plasma glucose levels? + why?
In severe hypoglycaemia. Provision of energy for emergencies and exercise.
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In what state do cortisol and growth hormone come in to act on plasma glucose levels?
In prolonged hypoglycaemia.
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Which 2 hormones have an indirect effect on gluconeogenesis?
Adrenaline and growth hormone (both act to increase gluconeogenesis but indirectly).
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How do adrenaline and growth hormone have this indirect effect?
Via mobilisation of glycerol and non-esterified fatty acids.
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What does inappropriate glucose homeostasis lead to?
Diabetes mellitus (chronic hyperglycaemia).
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What is the most common endocrine disorder?
Diabetes mellitus.
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All of insulin, glucagon and somatostatin are ........... hormones that are made as ..................... then processed and packaged into .............. ............. .
peptide, pre-prohormones, secretory granules.
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Card 3

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Why does insulin have such a short half life?

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Card 4

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What does insulin gene transcription and translation initially produce?

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Card 5

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What happens to preproinsulin in order to form proinsulin?

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