Biochem - Glucose Management Flashcards
What is the main function of insulin?
To reduce blood glucose levels by promoting target tissues to undergo anabolism and increase glucose storage
Why is too much insulin a problem?
The brain cannot produce it’s own glucose so requires blood glucose
What determines when beta cells secrete insulin?
Describe the pathway for insulin secretion in a beta cell
Blood glucose levels
Glucose enters cell via GLUT2
Glucolysis = increased ATP
Opens ATP dependant K+ channels
Depolarises cell membrane
Increased Ca2+ influx
Ca2+ causes insulin to be released
What are the function of the A chain, B chain and C-peptide?
A + B chain -> form 3D structure which allows insulin to fit in receptors
C-peptide - doesn’t have a function
When insulin is bound to C-peptide what is it known as?
Proinsulin
What are the unique components of the beta cell that allow it to provide the right amount of insulin at the right time?
Glucokinase’s Km is within 4.5-5.5 and is v responsive to changes in blood sugar levels
Increased blood glucose breakdown is proportional to insulin secretion (look at insulin secretion pathway)
What happens to glucose stimulated insulin secretion in T1 and T2 diabetes?
T1 - v v few beta cells left so v little production
T2 - blood glucose is so high that change has v little impact on insulin production - desensitised - always high levels of insulin
What mechanisms underpin the biphasic release of insulin and how does this change in T2 diabetes?
1st phase = immediately avaliable insulin from RRP (readily releasable pol)
2nd phase = insulin that has to be prepared before release
T2 diabetes = flattens and weakens due to desensitisation
For each of the following types of diabetes what is the pathological cause?
T1
T2
Gestational
Maturity onset diabetes of the young (MODY)
Neonatal
T1 - AUTOIMMUNE destruction of beta cells
T2- insulin insensitivity due to constant high levels
Gestational - diabetes during pregnancy
MODY - destruction of beta cells but NOT autoimmune
Neonatal - mutations in glucose sensor mechanisms
What is DKA, how does it occur?
Diabetic ketoacidosis
Increased lipolysis (insulin normally inhibits) - more common in T1
Pancreatic islets consist of 3 main cell types what are they and what do they release?
- Alpha = glucagon
- Beta = insulin
- Delta = somatostatin
When body goes into hypoglycaemia describe what happens to hormone production in the pancreatic islets?
- Insulin production stops
2. Glucagon production begins
Describe the relationship between insulin secretion and insulin sensitivity in:
- normal population
- T2 diabetic
Increase sensitive, less insulin produced
Normal population - highly variable
T2 - decreased sensitivity and decreased production
When the pancreatic islets are analysed in a patient with long standing T2 diabetes, what is a classic sign?
Degranulation - v v little insulin detected in insulin vesicles
GLP-1 and GIP are incretins produced in the gut that amplify insulin secretion.
What cells produce them and where are they found?
L cells in distal intestine
What is meant by paracrine signalling?
Give an example of it occurring within the pancreatic islets
Cell releasing a substance that induces a reaction in a cell v close to it
e.g. somatostatin binding to alpha/beta cells and inhibiting the function
What happens to glucagon in T2 diabetes?
High all the time -> plays a role in continual hyperglycaemia
How does glucagon work to increase blood sugar levels?
Induces gluconeogenesis and glycogen catabolism in the liver
What is basal insulin levels?
50% of insulin secreted = basal insulin levels
50% = post-prandial = post meals
How can T1 and T2 be differentiated on histology?
T1 = insulitis = lymphatic inflitrate T2 = amyloidosis (aggregates of protein)
How is insulin used?
1x basal long acting insulin
Short acting after every meal based on CHO intake
What transplant surgery has recently started to be used in patients with uncontrolled diabetes/incapacitating emotional effects?
Will it make the patient insulin independent?
Pancreatic islet transplant
- easier and better tolerated than full pancreatic transplant
Not always but will stop incapacitating hypos
What effect do beta blockers have on insulin release?
Inhibit
What effect does somatostain have on insulin when released from pancreas?
Inhibits beta cell release of insulin
Decrease in insulin
