1a Glucose Homeostasis Flashcards
What is significantly impaired when glucose concentration falls below normal levels of 4-5mmol/L?
Cerebral function
What is glucose particularly important for?
The functioning of the central nervous system
What is hypoglycaemia?
Blood glucose concentration levels fall below a normal levels
What can happen if blood glucose concentration falls below 2mmol/L?
Unconsciousness, coma and ultimately death
What does persistent hyperglycemia result in?
Diabetes mellitus
What hormones act against hypoglycemia?
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
What is meant by a 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 are gap junctions?
They allow small molecules to pass directly between cells
What are tight junctions?
Create small intercellular spaces
What type of communication is found between the islet cells and what enables this?
Paracrine communication due to presence of gap junctions
What does insulin do?
Stimulates growth and development and reduces blood glucose
What affect does insulin secreted from the beta cells have?
Increased:
- Glycolysis
- Glycogenesis
- Glucose transport into cells via GLUT 4
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
Aside from glucose effects, what else does insulin do?
- Increased amino acid transport, protein synthesis and lipogenesis
- Decrease in lipolysis
What is released when blood glucose levels are lowered?
Alpha cells release glucagon
What affect does glucagon have?
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?
High affinity for glucose, thus plasma concentration of glucose is reflected in its intracellular concentrations in beta or liver cells
What does GLUT2’s low glucose affinity allow for?
Variable transport rate
Glucose transport increases following a meal when glucose levels are high
Is GLUT-4 insulin sensitive?
Yes
What is GLUT-4’s glucose affinity and what does this mean?
High glucose affinity
Insulin stimulates glucose uptake in muscle cells via GLUT4, where hexokinase converts it into G6P so the cell can use it for glycolysis or store it as glycogen
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
How is insulin released?
- Glucose is transported by GLUT2 into beta cells
- Glycolysis occurs via glucokinase to produce ATP
- ATP inhibits the K+ efflux pump so K+ remains in the cell, causing membrane depolarisation
- Ca2+ voltage gated channels open, and the Ca2+ influx triggers secretion of insulin
What is meant by a graded response of insulin production?
Insulin is 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 as GI hormones enhance insulin secretion
This is the incretin effect
Transcription of what gene produces 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?
Stimulates insulin and suppresses glucagon
What effect does glucagon like peptide 1 have?
Increases feeling of fullness by delaying gastric emptying
Why does GLP1 have a short half life?
Rapidly degraded by enzyme dipeptidyl peptidase 4
What is GLP1 used in the treatment of?
Type 2 diabetes mellitus
How is GLP1 used in treatment of T2DM?
People with T2DM have reduced GLP1 reserves
It helps people with obesity feel full which can reduce insulin insensitivity
What is meant by the first phase insulin release?
The first spike in insulin following an increase in blood glucose
What is the first phase insulin release (FPIR) in normal people vs those with T2DM?
In T2DM, insulin levels increase much less than a healthy individuals, and stay elevated
How does the insulin receptor work?
- Insulin binds to alpha subunit
- This causes a confirmational change in the tyrosine kinase domain of the beta subunit
- This causes the movement of GLUT-4 from the intracellular space to the 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 significantly larger and higher following giving oral glucose to patients compared to IV glucose
