Lecture 20 Flashcards
How is pre-pro insulin converted to insulin?
- The signal sequence targets the protein to the endoplasmic reticulum, from where it is packaged into secretory vesicles
- The signal sequence is cleaved off by a protease in the endoplasmic reticulum, generating pro insulin
- Disulphide bonds form between chain A and chain B of pro insulin
- Proteases then cleave at either end of chain C
- This then gives insulin which is chain A and B joined by disulphide bonds and a C peptide
How is the insulin hexamer stabalised?
By zinc ions
Where is the insulin hexamer stores?
In secratory vesicles
What happens to hexamers in the bloodstream?
They disassemble
What are the three main types of insulin?
- Short acting
- Intermediate action
- Long acting
Name the short acting insulin?
- Insulin aspart
- Insulin glulisine
- Insulin lispro
Name medium acting inslin
Isophane insulin
Name long acting insulin
Insulin detemir
Insulin glargine
What are biphasic insulin?
Pre mixed insulin preparations containing various combinations of short-acting insulin or rapid-acting insulin analogue together with an intermediate-acting insulin
What insulin is medium acting?
Humulin I - isophane
Why do Humulin I and Humulin S have different rates/duration of action?
Humulin I contains protamine, whereas Humulin S does not
Protamine causes clustering of insulin, limiting diffusion through capillary walls
What is protamine?
Protamine is a basic protein (positively-charged) that binds to negatively charged insulin and clusters insulin hexamers
Why is insulin administered via injection and not orally?
insulin would be degraded by proteases in the stomach and small intestine
How is insulin injected?
Subcutaneously - stomach, buttocks, thighs
Why are injection sites rotated?
To avoid lipohypertrophy
What is lipohypertrophy?
accumulation of lumps under the skin- this can lead to problems with absorption of insulin
How should insulin be stored?
All insulin should be stored below 25oC and ideally in the fridge
What are the three basic types of insulin regimen?
- Multiple daily injection basal–bolus insulin regimens
- Continuous subcutaneous insulin infusion (insulin pump therapy)
- One, two or three insulin injections per day
What is Multiple daily injection basal–bolus insulin regimens?
injections of short‑acting insulin or rapid‑acting insulin analogue before meals, together with 1 or more separate daily injections of intermediate‑acting insulin or long‑acting insulin analogue
What is Continuous subcutaneous insulin infusion ?
a programmable pump and insulin storage device that gives a regular or continuous amount of insulin (usually a rapid‑acting insulin analogue or short‑acting insulin) by a subcutaneous needle or cannula, and patient-activated bolus doses at meal times
What is the artificial pancreas?
is a “closed loop” system that continuously monitors glucose levels and uses the information to adjust the amount of insulin being administered by an insulin pump. Uses a continuous glucose monitor, where a sensor is inserted just under the skin to measure interstitial glucose levels. Measurements are used to determine amount of insulin delivered by a pump
What is Islet cell transplantation?
implanting islet cells from a deceased donor. Simple procedure where cells are injected through a catheter placed in the upper abdomen into the liver
What are the strategies for improving therapeutic outcomes in Type 1 diabetes
- The artificial pancreas
- Islet cell transplantation
- Stem cell-derived beta cells
- Re-purposing of cells in the patient
What is re purposing of cells in the patient?
Switching off a single gene in GI cells allowed them to produce insulin.
Gut endocrine progenitor cells could be differentiated into glucose-responsive insulin-producing cells by ablation of the transcription factor Fox01
