1a Glucose Homeostasis Flashcards
What is significantly impaired when glucose concentration falls below normal levels?
Cerebral function
What bodily system is glucose particularly important for?
The functioning of the central nervous system
What is hypoglycemia?
Blood glucose concentration levels fall below a normal levels
What can happen is blood glucose Concentration falls below 2mmol/L
Unconsciousness, coma and ultimately death
What does persistent hyperglycemia result in?
Diabetes mellitus type II
What hormones act against hypoglycemia? - 4
Glucagon
Cortisol
Growth hormone
Catecholamines
What is the most prevalent form of diabetes?
Type 2 diabetes mellitus
What are the three types of diabetes
Type 1 DM
Type 2 DM
maturity onset diabetes of the young
state the cell types found in the pancreas - 2
Islets of Langerhans
Exocrine acinar cells
What is meant by the pancreas having retroperitoneal structure?
Has a peritoneum on the anterior side only
What are the small clumps of cells in the pancreas called?
Islets of Langerhans
What are exocrine acinar cells?
Cells that generate exocrine secretions
What are the three types of islet cells?
alpha, beta and delta cells
What are the alpha cells involved with?
Glucagon secretion
What are the beta cells in the islets of langerhans involved with?
Insulin secretion
What are the delta cells in the islet of langerhans involved with?
Somatostatin secretion
What do the gap junctions between the cells of the islets of Langerhans allow?
They allow small molecules to pass directly between cells - paracrine communication
What is the purpose of the tight junctions between the cells of the islets of langerhans?
Create small intercellular spaces
What effect does somatostatin have on the insulin and glucagon?
inhibitory
What type of communication is found between the islet cells?
Paracrine communication
What does insulin do?
Stimulates growth and development and reduces blood glucose
What increased effect does insulin secreted from the beta cells have on the liver? - 5
Increased:
- Glycolysis
- Glycogenesis
- Glucose transport into cells via GLUT 4
- amino acid transport
- lipogenesis
Where is GLUT 4 predominantly expressed?
Adipocytes and skeletal muscle
When blood glucose is high, what is released?
Insulin from the beta cells as well as some glucagon from the alpha cells to ensure that hypoglycaemia doesn’t occur
How does somatostatin affect the release of insulin from beta cells when there is a rise in blood glucose?
inhibits the release of insulin
How does glucagon affect the release of insulin from beta cells when there is a rise in blood glucose?
stimulates release of insulin
state the impact of insulin on:
amino acid transport
protein synthesis
lipogenesis?
Increases amino acid transport, protein synthesis and lipogenesis
What is released when blood glucose levels are lowered?
Alpha cells release glucagon
What affect does glucagon have? - 5
INCREASED:
- gluconeogenesis
- lipolysis
- blood glucose
- amino acid transport to the liver
- hepatic glycogenolysis
Is GLUT 2 insulin sensitive?
No
What is the main glucose sensor?
Glucokinase (hexokinase as IV)
What is GLUT 2’s affinity for glucose, and what does this mean?
LOW affinity for glucose => moves glucose into liver cell in proportion to plasma glucose levels
Does glucose 6 phosphate inhibit glucokinase?
No
Why do glucose 6 phosphate levels give a good indication of glucose levels as well?
Glucose to glucose 6 phosphate is a continual conversion by glucokinase therefore the amount of glucose present is equal to glucose 6 phosphate
What intrabodily changes lead to insulin release
The ATP produced from glycolysis inhibits the potassium ion channels, meaning K+ remains in the beta cells
therefore, there is an intracellular influx of Ca2+ which triggers the insulin to be released from the beta cells
What is meant by a graded response of insulin production?
Insulin isn’t released in an all or nothing manner, continually released when needed and the amount released changes over time
What is pro insulin cleaved into?
insulin and C-peptide
What happens to C peptide levels after a big meal?
Increase
What happen to someone’s C peptide levels when a person with type 1 diabetes eats a meal?
They are low - this is because C peptide levels are only a measure of endogenous insulin, and doesn’t include the insulin which they have injected following the meal
What is the difference between oral and intravenous glucose in terms of plasma insulin production? And what is this effect called?
Oral is significantly higher - incretin effect
Transcription of what gene produced Glucagon like peptide 1?
Pro-glucagon gene
Where is glucagon like peptide found?
In the gut
What is the effect of glucagon like peptide 1?
Stimulated insulin and suppresses glucagon
What effect does glucagon like peptide1 do to us?
Increases feeling of fullness
Why does GLP1 have a short half life?
Rapidly degraded by enzymes dipeptidyl peptidase 4
What is GLP1 used in the treatment of?
Diabetes mellitus
What is meant by the first phase insulin release?
This is following a meal, when a diabetics insulin levels do increase slightly, but much less than a healthy individuals, and stay elevated
How does the insulin receptor work?
- Insulin binds to alpha subunit
- Causes a confirmation change in the tyrosine kinase domain of the beta sun unit
- This causes the movement of GLUT 4 from intracellular space to cell membrane so glucose can be absorbed
What part of the insulin receptor does insulin initially bind to?
Extracellular domain - alpha subunit
What percentage of the pancreas gland is involved in exocrine secretions?
98%
Where may you find insulin receptors?
Liver, muscle and fat
What is the incretin effect?
When the production of plasma insulin is greater following giving oral glucose to patients rather than IV
impact of insulin on lipolysis
decreases
why do we see an increase in amino acid transport to the liver by glucagon?
amino acid metabolites are used as substrates in gluconeogenesis to produce glucose
How do PNS activity affect the secretion of insulin when there is a rise in blood glucose?
stimulates the release of insulin
How do SNS activity affect the secretion of insulin when there is a rise in blood glucose?
inhibits secretion of insulin via alpha cells
relationship between insulin and glucagon
insulin inhibits glucagon release
is GLUT-4 insulin sensitive and what is its glucose affinity?
YES, and has high glucose affinity
link between insulin and GLUT-4
insulin stimulates the uptake of glucose by GLUT-4
what does glucokinase serve as in beta-cells?
a glucose sensor
What is the main difference in the actions of hexokinase I and hexokinase IV?
Hexokinase IV is not subject to -ve feedback from Glucose-6-P
Describe the process by which insulin is released from the beta cells after blood glucose increases?
- Glucose transported into beta cell by GLUT-2 (which is NOT insulin sensitive and has a low glucose affinity)
- Glucose in the cell undergoes glycolysis by Glucokinase (hexokinase IV) to produce ATP (Rate-Limiting Step)
- ATP inhibits the K+ efflux pump so K+ remains intracellularly and builds up in the cell, this relative increase leads to **membrane depolarisation
- This opens Ca2+ voltage gated channels leading to Ca2+ influx which promotes secretion of stored insulin in beta cell
In what form is insulin stored in the body
proinsulin
Why is measuring endogenous c-peptide a good indicator for insulin?
c-peptide can be stable for up to half an hour when samples sent to lab
A person with Type 1 diabetes mellitus eats a Big Mac meal, do you expect their C-Peptide levels to be high or low?
low
What is the gastrointestinal incretin effect?
GI hormones enhance insulin secretion so when glucose is ingested orally there’s higher plasma insulin in oral vs IV even though plasma glucose is the same
What is Glucagon like peptide-1 (GLP-1)?
gut hormone
What is GLP-1 secreted in response to?
Secreted in response to nutrients in gut
What effects does GLP-1 have on the INSULIN secreted by the islets of langerhans?
stimulates insulin
What effects does GLP-1 have on the GLUCAGON secreted by the islets of langerhans?
suppresses glucagon
link between GLP-1 and Type II diabetes
T2 diabetics have low GLP-1
link between GLP-1 and Type II diabetes
T2 diabetics have low GLP-1
How does the insulin receptor work when insulin binds? (3)
- Insulin binds to the extracellular domain of insulin receptor at the alpha subunit
- This causes a conformational change in the tyrosine kinase domains of the beta-subunits
- This enables GLUT4 transport from intracellular into the membrane
What is the first phase insulin release (FPIR) in normal people vs those with T2DM?
normal people => marked increase in insulin after IV glucose challenge and then blood gluc goes down and thus so does insulin
T2DM this response is blunted so it’s not just that our cells are resistant to insulin, but also beta cells can’t produce enough insulin to counteract glucose load after working hard for a long time
What is the first phase insulin release (FPIR) in normal people vs those with T2DM?
normal people => marked increase in insulin after IV glucose challenge and then blood gluc goes down and thus so does insulin
T2DM this response is blunted so it’s not just that our cells are resistant to insulin, but also beta cells can’t produce enough insulin to counteract glucose load after working hard for a long time
What is the first phase insulin release (FPIR) in normal people vs those with T2DM?
normal people => marked increase in insulin after IV glucose challenge and then blood gluc goes down and thus so does insulin
T2DM this response is blunted so it’s not just that our cells are resistant to insulin, but also beta cells can’t produce enough insulin to counteract glucose load after working hard for a long time
