Glucose Homeostasis Flashcards
What classes as hypoglycaemia?
when blood glucose falls below normal levels of 4-5mmol/L
What happens to cerebral function during hypoglycaemia?
it is increasingly impaired
what happens if blood glucose concentration falls below 2mmol/L?
unconsciousness, coma and death
what blood glucose concentration range is classed as normoglycaemic?
4-7mmol/L
Which 4 hormones are involved in increasing our blood glucose from a low level?
glucagon - pancreas
cortisol
GH - growth hormone
catecholamines
which cells in the pancreas are involved in exocrine secretions? What are exocrine secretions? What percentage of the pancreas does this?
exocrine acinar cells
enzymes that help with digestion
98%
How are exocrine secretions secreted?
via duct to small intestine
what percentage of the pancreas is made up of islets of langerhans?
2%
what do alpha cells secrete?
glucagon
what do beta cells secrete?
insulin
what do delta cells secrete?
somatostatin
what is a gap junction?
allows small molecules to pass directly between cells
what is a tight junction?
small intercellular spaces
what is the function of insulin?
reduce blood glucose, stimulate growth and development
what is the function of glucagon?
increases blood glucose
what is the function of somatostatin?
inhibits both insulin and glucagon
which factors other than blood glucose stimulate the beta cells to secrete insulin?
some amino acids
some GI hormones
parasympathetic nervous system activity (digestion)
what effect does the sympathetic nervous system have on beta cells?
decreases insulin secretion via alpha cells by switching off their receptors
some minor stimulation by beta adrenergic receptors
What does insulin cause?
build up of glycogen stores breakdown of glucose uptake of glucose increases amino acid transport increases protein synthesis reduces breakdown of fat and increases storage of fat
which factors increase glucagon?
decrease in blood glucose some amino acids some Gi hormones SNS activity via alpha cells PNS activity
what does glucagon do?
Increase breakdown of fats to form more glucose
Increase amino acid transport into the liver to form more glucose (gluconeogenesis)
helps break down glycogen stores in the liver (hepatic glycogenolysis)
Is GLUT-2 transporter insulin sensitive?
no
how is glucose first metabolised once it enters the cell?
What is it eventually converted into?
converted to glucose-6-phosphate by hexokinase IV (glucokinase) - this is the rate limiting step as it depends on how much glucose is in the blood
ATP
What does ATP do to ATP sensitive K+ channels during glucose uptake into beta cells and what affect does this have on the cell?
blocks them
which leads to increase in intracellular K+ levels, causing depolarisation
which stimulates Calcium voltage gated channels which causes influx of calcium ions
how does influx of calcium affect the beta cell?
causes release of insulin and synthesis of insulin
what do we usually measure when we want to test someone’s ability to produce their own insulin and why/
c-peptide
insulin assays aren’t as stable and more difficult to measure, c-peptide is easier to determine
c-peptide is the by-product produced during proteolytic cleavage of proinsulin
what is the ‘incretin’ effect?
more insulin is released when glucose is given orally than when glucose is given intravenously due to the increased release of gut hormones that stimulate insulin release
which is the key hormone involved in the incretin effect?
glucagon like peptide-1 (GLP-1)
when is GLP-1 secreted and how is it produced?
in response to nutrients in the gut
transcription product of pro-glucagon gene, mostly from L-cell within stomach
How does GLP-1 work?
stimulates insulin, suppresses glucagon
increases satiety
why does GLP-1 have a short half life?
due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4)
what are GLP-1 levels like in people with diabetes mellitus?
low
how can we utilise GLP-1?
administer injections to individuals with diabetes to promote satiety and increase insulin secretion
what is first phase insulin release and how does it differ in those with diabetes?
release of stored insulin
people with type 2 diabetes have less stored insulin and have to synthesise new insulin which they cannot secrete fast enough to make a surge
which part of the insulin receptor does insulin bind to?
what happens?
extracellular domain (because it is a very large peptide) of alpha subunit causes a conformational change in the tyrosine kinase domains of the beta subunits
