Lecture 20

Question 1

How is pre-pro insulin converted to insulin?

Answer 1

• 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

Question 2

How is the insulin hexamer stabalised?

Answer 2

By zinc ions

Question 3

Where is the insulin hexamer stores?

Answer 3

In secratory vesicles

Question 4

What happens to hexamers in the bloodstream?

Answer 4

They disassemble

Question 5

What are the three main types of insulin?

Answer 5

• Short acting
• Intermediate action
• Long acting

Question 6

Name the short acting insulin?

Answer 6

• Insulin aspart
• Insulin glulisine
• Insulin lispro

Question 7

Name medium acting inslin

Answer 7

Isophane insulin

Question 8

Name long acting insulin

Answer 8

Insulin detemir
Insulin glargine

Question 9

What are biphasic insulin?

Answer 9

Pre mixed insulin preparations containing various combinations of short-acting insulin or rapid-acting insulin analogue together with an intermediate-acting insulin

Question 10

What insulin is medium acting?

Answer 10

Humulin I - isophane

Question 11

Why do Humulin I and Humulin S have different rates/duration of action?

Answer 11

Humulin I contains protamine, whereas Humulin S does not
Protamine causes clustering of insulin, limiting diffusion through capillary walls

Question 12

What is protamine?

Answer 12

Protamine is a basic protein (positively-charged) that binds to negatively charged insulin and clusters insulin hexamers

Question 13

Why is insulin administered via injection and not orally?

Answer 13

insulin would be degraded by proteases in the stomach and small intestine

Question 14

How is insulin injected?

Answer 14

Subcutaneously - stomach, buttocks, thighs

Question 15

Why are injection sites rotated?

Answer 15

To avoid lipohypertrophy

Question 16

What is lipohypertrophy?

Answer 16

accumulation of lumps under the skin- this can lead to problems with absorption of insulin

Question 17

How should insulin be stored?

Answer 17

All insulin should be stored below 25oC and ideally in the fridge

Question 18

What are the three basic types of insulin regimen?

Answer 18

• Multiple daily injection basal–bolus insulin regimens
• Continuous subcutaneous insulin infusion (insulin pump therapy)
• One, two or three insulin injections per day

Question 19

What is Multiple daily injection basal–bolus insulin regimens?

Answer 19

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

Question 20

What is Continuous subcutaneous insulin infusion ?

Answer 20

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

Question 21

What is the artificial pancreas?

Answer 21

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

Question 22

What is Islet cell transplantation?

Answer 22

implanting islet cells from a deceased donor. Simple procedure where cells are injected through a catheter placed in the upper abdomen into the liver

Question 23

What are the strategies for improving therapeutic outcomes in Type 1 diabetes

Answer 23

• The artificial pancreas
• Islet cell transplantation
• Stem cell-derived beta cells
• Re-purposing of cells in the patient

Question 24

What is re purposing of cells in the patient?

Answer 24

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

Question 25

What are stem cell derived beta cells?

Answer 25

Stem cell-derived beta cells have been produced from human pluripotent stem cells. These cells formed islet-like clusters and made insulin when transplanted into mice
Using beta cells derived from stem cells overcomes the limitation of acquiring islets from donors