Endocrine Pancreas 1 Flashcards
Body energy =
energy intake - energy ouput
Energy (food) intake is determined by balance of activity of which 2 hypothalamic centres?
Feeding centre
Satiety centre
What is the function of the feeding centre?
Promotes feelings of hunger and drive to eat
What is the function of the satiety centre?
Promotes feelings of fullness by suppressing the feeding centre
What is the glucostatic theory?
Food intake is determined by blood glucose: as [BG] increases, the drive to eat decreases (-feeding centre; +satiety centre)
What is the lipostatic theory?
Food intake is determined by fat stores: as fat stores increase, the drive to eat decreases (-feeding centre; +satiety centre)
What part does leptin play in the lipostatic theory?
Leptin is a peptide hormone released by fat stores which depresses feeding activity (not the only signal in the system, as obesity proves…)
What can result from disruption of these pathways?
Obesity
What are the 3 categories of energy output?
Cellular work
Mechanical work
Heat loss
Describe cellular work
transporting molecules across membranes; growth + repair; storage of energy (e.g. fat, glycogen, ATP synthesis)
Describe mechanical work
movement, either on large scale using muscle or intracellularly
Describe heat loss
associated with cellular and mechanical work - accounts for half of our energy output
What is the only part of energy output we can regulate voluntarily?
Mechanical work
What is metabolism?
Integration of all biochemical reactions in the body
What are the 3 elements of metabolism?
- extracting energy from nutrients in food
- storing that energy
- utilising that energy for work
Describe anabolic pathways
‘BUILD UP’
net effect is synthesis of large molecules from smaller ones, usually for storage purposes
Describe catabolic pathways
‘BREAK DOWN’
net effect is degradation of large molecules into smaller ones, releasing energy for work
What state do we enter after eating?
Absorptive state
Describe the absorptive state
state where ingested nutrients supply the energy needs of the body and excess is stored = anabolic
What state do we enter between meals and overnight?
Post-absorptive state
Describe the post-absorptive state
The pool of nutrients in the plasma decreases and we enter this state where we rely on body stores to provide energy = catabolic
What is the brain described as?
‘Obligatory Glucose Utiliser’ !!
What substances can the brain use for energy?
ONLY glucose
Not fats, carbs or protein like other cells
Due to the brain being an OGI, in the post-absorptive state, even tho no new carb is gained, we must…
maintain blood glucose concentration sufficient to meet the brain’s requirements
What does failure to maintain blood glucose concentration in the post-absorptive state result in?
Hypoglycaemia which can lead to coma and death
How is blood glucose maintained?
By synthesising glucose from glycogen (glycogenolysis) or amino acids (gluconeogenesis)
In hyperglycaemia (like in diabetics), what does the body do with the excess glucose?
Tries to eject it via urine
How is glucose stored in the body?
As glycogen, which is stored in the liver and turns it to fat
What is the NORMAL range of blood glucose?
4.2 - 6.3mM
remember 5 mmoles !!
What BG level is considered hypo- and hyper- glycaemia?
Under 4 is too low, under 3 is emergency
Around 10/11 is hyper - symptoms develop slowly
Where in the pancreas are hormones released?
Islets of Langherhans
What are the 4 types of islet cells in the pancreas?
Alpha
Beta
Delta
F
What hormones do each of the pancreatic islet cells produce?
alpha = GLUCAGON beta = INSULIN delta = SOMATOSTATIN F = pancreatic polypeptide (function unknown - may help control nutrient absorption from GIT)
What is the fed (absorptive) state dominated by?
INSULIN
Name 4 processes which increase in the fed state due to insulin
Glucose oxidation Glycogen synthesis Fat synthesis Protein synthesis (BG decreases)
What is the fasted (post-absorptive) state dominated by?
GLUCAGON
Name 3 processes which increase in the fasted (post-absorptive) state when glucagon dominates
Glycogenolysis
Gluconeogenesis
Ketogenesis
(BG decreases)
What does insulin stimulate?
Glucose uptake by cells
How is insulin synthesised?
As a large preprohormone (preproinsulin), which is then converted to proinsulin in the ER
What is the next stage when proinsulin in made?
It is then packaged as granules in secretory vesicles; within these vesicles proinsulin is cleaved again to give insulin + C-peptide
What then happens to insulin and C-peptide?
It is stored in this form until the B cell is activated and secretion occurs
What does this step by step process of insulin synthesis and storage tell us about the type of hormone it is?
It is a peptide hormone
During the absorptive state, what three things enter the blood from the GI tract?
Glucose
Amino acids
Fatty acids
Both glucose and aa’s stimulate insulin secretion, but what is the major stimulus?
Increase in blood glucose concentration
Insulin is the ONLY hormone that does what?
Lowers BG
Where is excess glucose stored?
As glycogen in liver and muscle As triacyglycerols (TAG) in liver and adipose tissue
How are amino acids used?
Mainly to make new proteins; also as energy source
How are excess amino acids stored?
They are converted to fat
How are excess fatty acids stored?
In the form of triglycerides in adipose tissue and liver
Describe in a stepwise manner the control of insulin secretion in situations of high BG
- High BG level in blood
- Glucose enters cells through GLUT and metabolism increases
- Increased ATP in cell triggers closure of K-ATP channels
- Intracellular K+ rises and depolarises the cell
- Voltage dependent Ca2+ channels open and trigger insulin vesicle exocytosis
Describe in a stepwise manner the control of insulin secretion in situations of low BG
- Low BG level in blood
- K-ATP channels remain open so K+ ions flow out removing +ve charge from cell
- Cell is hyperpolarised
- Voltage-gated Ca2+ channels remain closed and insulin is not secreted
So what is the main driving force for the release of insulin?
Glucose
What is the primary action of insulin?
Binds to tyrosine kinase receptors on the cell membrane of INSULIN-SENSITIVE tissues to increase glucose uptake by these tissues
In muscle + adipose, insulin stimulates mobilisation of…
SPECIFIC glucose transporters (GLUT-4) via a signal tranduction cascade
Where do GLUT-4 transporters reside?
Cytoplasm of cells
What does GLUT-4 do when stimulated by insulin?
Secretory vesicle migrates to membrane and GLUT-4 is then able to transport glucose into the cell
What do GLUT-4 transporters do when insulin stimulation stops?
They return to the cytoplasmic pool
What is glucose taken up by cells primarily used for?
Energy
What 2 types of tissue are insulin DEPENDENT? (where other types of tissue do not require it to take up glucose)
Muscle
Fat
Why are other tissues not insulin dependent?
They have other types of GLUT transporters (not GLUT-4)
How do beta cells of pancreas and liver take up glucose?
GLUT-2 transporters
Does insulin directly affect the liver?
No
Does insulin status affect glucose transport into hepatocytes tho?
Yea
In the fed state, how does insulin impact glucose transport in hepatocytes?
Liver takes up glucose cos insulin activates hexokinase which lowers IC glucose creating a gradient favouring gluocose movement into cells
In the fasted state, what does the liver do to increase BG?
Synthesises glucose via glucogenolysis and gluconeogenesis
Name 6 more actions of insulin (5 are anabolic/inhibit catabolism)
- Increases glycogen synthesis in muscle + liver
- Increases amino acid uptake into muscle
- Increases protein synthesis + inhibits proteolysis
- Increases triacyglycerolsynthesis in adipocytes + liver
- Inhibits the enzymes of gluconeogenesis in the liver
- Promtotes K+ ion entry into cells by stimulating Na+/K+ ATPase
How are all of the additional roles of insulin possible?
Activation of multiple signal transduction pathways associated with the Insulin Receptor
What is the half life of insulin?
5 mins
Once insulin action is complete, what happens to insulin-bound receptors?
They are internalised by endocytosis and destroyed by insulin protease (some recycled)
Name 5 stimuli which increase insulin release
- Increased BG
- Increased plasma amino acids
- Glucagon
- Other (incretin) hormones controlling GI secretion + motility
- Vagal nerve activity
Give examples of other incretin hormones controlling GI secretion + activity
Gastrin, secretin, CCK, GLP-1, GIP (released by jejunum and ileum in response to nutrients)
Why is glucagon a stimuli for insulin?
Insulin is required to take up glucose created via gluconeogenesis stimulated by glucagon
What is the purpose of incretin hormones and vagal activity stimulating insulin release?
Anticipatory phase - preparation for food
Name 4 stimuli which inhibit insulin release
- Low BG
- Somatostatin (GHIH)
- Sympathetic alpha 2 effects
- Stress (e.g. hypoxia)
What does vagal activity stimulate the release of?
Major GI hormones
Insulin
What does vagal activity stimulating the release of major GI hormones and insulin mean in terms of glucose administration?
Insulin response to an IV glucose load is less than the equivalent amount of glucose administered orally
Why is insulin response to an IV glucose load less than the equivalent amount of glucose administered orally?
Because oral loading of glucose stimulates insulin release both by direct effect on beta cells AND VAGAL STIMULATION of beta cells (PLUS incretin effects)
