The endocrine pancreas 1+2 Flashcards
Body energy = energy intake - ?
energy output
the 2 hypothalamic centres which determine energy intake
feeding centre
satiety centre
Feeding centre
promotes feeling of hunger and drive to eat
satiety centre
promotes feeling of fullness by suppressing the feeding centre
What 3 things control activity in the 2 hypothalamic centres which determine energy intake?
neural signals
chemical signals
presence of chemicals in the plasma
What is the glucostatic theory?
food intake is determined by blood glucose
as BG increases, drive to eat decreases, inhibit feeding centre and stimulate satiety centre
What is the lipostatic theory?
food intake is determined by fat stores
as they increase, drive to eat decreases, inhibit feeding centre and stimulate satiety centre
What hormone is linked to the lipostatic theory and what is its function?
Leptin
peptide hormone which is released by fat stores which depresses feeding activity
What will occur if these 2 hypothalamic centres are disrupted? What are other common causes of this?
obesity
more often due to just eating too much and not exercising enough
What are the 3 types of energy output
cellular work
mechanical work
heat loss
What is the only part of our energy output which we can regulate?
mechanical work - large scale eg muscle
Define metabolism
integration of all biochemical reactions in the body
The 3 parts of metabolism are
extracting energy from food
using that energy
storing energy
Is catabolism or anabolism linked to storage?
anabolism
What is the absorptive state?
after eating - ingested nutrients supply energy needs and excess is stored
Is the absorptive state anabolic or catabolic phase?
anabolic
What is the post-absorptive state?
between meals/overnight pool of nutrients in plasma decreases - fasted state
Is the post-absorptive state anabolic or catabolic phase?
catabolic
What organ is named as the main obligatory glucose utiliser?
brain
What other energy source can the brain use and when?
ketone bodies
starvation
What happens if in the post-absorptive state, Bg is not maintained?
hypoglycaemia
How is BG maintained in the post - absorptive state?
gluconeogenesis and glycogenolysis
What is gluconeogenesis?
make new glucose from amino acids
What is glycogenolysis?
making glucose from glycogen
Normal [BG]?
5mM
Hypoglycaemia [BG]?
< 3mM
What 2 hormones tightly regulate [BG]?
insulin and glucagon
Where are the 2 endocrine hormones produced in the pancreas and what % of the pancreas is endocrine?
islets of Langerhans
1%
What is the blood supply to the islets of Langerhans?
copious
4 types of islets of Langerhans and what they produce
alpha = glucagon beta = insulin delta = somatostatin F = pancreatic polypeptide
What Is insulin?
A peptide hormone secreted by pancreatic beta cells which stimulates glucose uptake by cells
What are the different molecules names in the formation of insulin?
preproinsulin
proinsulin
insulin and c peptide
How is insulin stored?
in a vesicle as insulin and c peptide until activated
What is the major stimulus for insulin secretion?
[BG] increase
What is the only hormone which can lower [BG]?
insulin
What state (absorptive or post-absorptive) does insulin dominate?
absorptive
Why do most cells use glucose as energy source during the absorptive state?
Easy to metabolise
How is excess glucose stored? (2 ways)
glycogen in liver and muscle
TAG in adipose tissue and liver
What happens to excess amino acids?
converted to fat
What happens to excess fatty acids?
TAG in liver and adipose tissue
What specific ion channels do beta cells have and what are they sensitive to?
K+
[ATP]
How do K+ ion channels in beta cells work to release insulin ultimately?
glucose enters through GLUT after a meal metabolism and [ATP] increases K-ATP closes and cell depolarises voltage dependent calcium channels open calcium causes exocytosis of insulin
What receptors does insulin bind to and on what kind of tissues?
tyrosine kinase
insulin sensitive –> muscle and fat
Insulin stimulates the mobilisation of what kind of transporters?
GLUT-4
Where do GLUT-4 transporters live?
cytoplasm of unactivated muscle and adipose tissue
GLUT-1 transports…
basal glucose uptake into many tissues eg brain, RBC, kidney
Where are GLUT-2 transporters found?
b cells of pancreas and liver
What are the 3 GLUT non insulin dependent receptors?
1.2.3
Is the liver insulin sensitive?
no
What GLUT receptors does the liver use?
GLUT 2
How does insulin effect glucose transport into the liver?
glucose enters down concentration gradient
glucose transport into hepatocytes is enhanced by insulin status
Why does insulin have an effect on glucose transport into liver?
hexokinase enzyme lowers [glucose] in the cell and forms a concentration gradient in favour of glucose entering into the hepatocytes
List some other anabolic functions of insulin
glycogen synthesis in muscle and liver amino acid uptake into muscle protein synthesis TAG synthesis in adipocytes and liver inhibits gluconeogenic enzymes
List 2 other actions of insulin which are due to activation of multiple transducer pathways
permissive effect on HGH
promotes K+ entry into cells
Insulin half-life and what is it degraded by?
5 mins
liver and kidneys
What happens to insulin bound receptors when insulin action is complete?
endocytosed
destroyed by insulin protease
Stimuli which increase insulin release
increase [BG] glucagon vagal nerve activity increased amino acids in plasma incretin hormones eg CCK
Stimuli which inhibit insulin release
decreased [BG]
somatostatin
stress eg infection
sympathetic alpha 2 effects
Why does glucagon increase insulin release?
insulin required to take up glucose created via gluconeogenesis stimulated by glucagon
Why does vagal activity increase insulin release and discuss iv vs oral glucose
parasympathetic - GI hormones
incretin hormones increase insulin
oral glucose better due to direct effect + incretin hormones and vagal stimulation of B cells
What is glucagon?
peptide hormone produced by alpha cells of the pancreatic islets and is a glucose mobilising hormone
What organ does glucagon primarily act upon?
liver
Half life of glucagon and what is it degraded by?
5-10 mins
liver
What 4 hormones make up the glucose counter regulatory system?
glucagon
HGH
cortisol
epinephrine
When is glucagon most active?
post-absorptive state
Receptors for glucagon?
GPCR to adenylate cyclase/cAMP
When glucagon receptors are activated what happens?
phosphorylate specific liver enzymes
3 consequences of phosphorylation of specific liver enzymes
increased gluconeogenesis
increased glucogenolysis
formation of ketones from FA
What is the net result of glucagon action on the liver enzymes?
increased [BG]
What is the pattern of glucagon secretion and when does this increase?
constant
when [BG] < 5.6mM
Why do amino acids also stimulate glucagon aswell as insulin release?
adaption for high protein meal
prevent hypoglycaemia
How is glucose spared for the brain in the post absorptive state?
lower insulin
muscle and fat cannot readily access glucose
glucose sparing for brain
Stimuli that promote glucagon release
low [BG] amino acids in plasma sympathetic innervation and epinephrine, B2 effect cortisol stress
Stimuli that inhibit glucagon release
insulin
glucose
somatostatin
FFA and ketones
Parasympathetic effect on islet cells
increase insulin, to a less degree glucagon
vagus - anticipatory phase of digestion
Sympathetic effect on islet cells
increase glucose mobilisation
increase glucagon and epinephrine and inhibit insulin
What is somatostatin?
peptide hormone produced by D cells in pancreas and hypothalamus , also known as GHIH.
How does somatostatin act?
slow down absorption in Gi tract to prevent surges
prevents glucagon and insulin
How can somatostatin be used clinically (GI)
diarrhoea and tumours who have symptoms of diabetes
What does exercise do to glucose uptake?
increase in muscle without insulin being present by increasing insulin sensitivity of muscle
What happens with GLUT-4 receptors and what are long term effects of exercise?
increase in number and migrate to cell surface without insulin
effect persists and long term effects if regular exercise
How are ketone bodies formed?
in starvation FFA are formed from adipose tissue and make ketone bodies by conversion in the liver
What 2 parts of the body are ketone bodies used by?
brain and muscle
Benefit of ketone bodies
spares the protein which would be broken down in starvation
What is diabetes mellitus?
loss of control of blood glucose levels
What is type 1/IDDM diabetes?
autoimmune destruction of the pancreatic b cells
destroys ability to produce insulin and compromises ability to absorb glucose
Treatment of type 1 diabetes
need insulin injections every day
What is ketoacidosis?
similar to starvation - lack of access to nutrients
lack of insulin depresses ketone body uptake
Harm of ketoacidosis
build up in blood - acidic
life threatening and death
2 ways ketones are detectable
urine
acetone breath
What is type 2 diabetes?
insulin resistance of peripheral tissues and fat and muscle no longer respond to normal insulin levels
2 reasons why fat and muscle no longer respond to insulin
reduced number of receptors
abnormal response of insulin receptors
What happens to b cells in type 2 diabetes?
nothing - still intact
may even be hyperinsulinaemia
What is type 2 diabetes associated with?
obesity, diet, exercise
Usual age for type 2 diabetes
> 40 but decreasing
Treatment of type 2 diabetes
diet and exercise
oral hypoglycaemic drugs eg metformin
sulphonylureas
Why can type 2 diabetes treatments not be used in type 1?
requires functioning b cells
Diagnostic criteria for diabetes
hyperglycaemia
What test is done to diagnose diabetes?
glucose tolerance test
Why is [BG] increased in type 1 and type 2 diabetes?
type 1 - inadequate insulin release
type 2 - inadequate tissue response
Briefly describe how a glucose tolerance test would be done
patient ingests glucose after fasting
[BG] should return to fasting in an hour
if not returned by 2 hours is diabetic
How to convert to mM from mg/dl?
divide by 18
Why are there risks associated with hyperglycaemia?
glucose is a highly reactive molecule
4 hyperglycaemia complications
retinopathy
neuropathy
nephropathy
CVD
Who is especially at risk of diabetic hypoglycaemia?
type 1 on exogenous insulin
How is hypoglycaemia staged?
changes in [BG]
