1a Glucose Homeostasis Flashcards
What is significantly impaired when glucose concentration falls below normal levels?
Cerebral function
What 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
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?
Paracrine communication
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?
Increase 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, so whatever glucose is in our blood stream is therefore reflected in the intracellular concentration of the beta cell
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?
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?
Pro 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 - increatin 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
Wh6 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 significantly larger and higher following giving oral glucose to patients
