Insulin - TPB

Question 1

What is the isoelectric point of insulin?

Answer 1

insulin has an isoelectric point of 5.3 in the denatured state
- is negatively charged at neutral pH

pH < pI = positive charge
pH > pI = negative charge

Question 2

What happens to insulin in the presence of divalent metal ions?

Why do commercial insulin preparations contain phenolic excipients?

Answer 2

insulin can associate into hexameric complexes in the presence of divalent metal ions such as zinc
- stabilises insulin

commercial insulin preparations contain phenolic excipients such as phenol and m-cresol as antimicrobial agents
- stabilises insulin increasing its shelf life

Question 3

What is normal insulin physiology?

Answer 3

normal human pancreas secretes approx 1 unit of insulin per hour to maintain basal glycemic control

normal physiology of basal concentrations are supplemented by large prandial insulin spikes

Question 4

What are the factors determining insulin use?

Answer 4

onset of action
peak time
duration in the body

Question 5

What is NPH insulin?

Answer 5

NPH insulin = isophane insulin

is a neutral crystalline suspension prepared by cocrystallisation of insulin with protamine for prolonged action
- intermediate acting

Question 6

What is Lente insulin?

Answer 6

lente insulin is a zinc insulin suspension for single daily injection
- is a mixture of two insoluble forms of insulin
= rhombohedral zinc insulin crystals and amorphous insulin particles

zinc is used as a delayed agent
- reduces the solubility of insulin

Question 7

How is insulin glargine long acting?

Answer 7

it microprecipitates after subcutaneous injection
- crystal dissolves slowly to release insulin glargine with full activity after 4-5 hours and sustained to 24 hours
- no significant peak

Question 8

How is insulin detemir long acting?

Answer 8

has a covalent link to a fatty acid that enhances binding to albumin
- is released at a constant rate over 24 hours

Question 9

What is recombinant DNA technology?

Answer 9

process for the production of a biological product using DNA
- proteins, hormones, enzymes

production is via laboratory engineered DNA sequences inserted into a plasmid DNA

Question 10

What is the rationale for recombinant human insulin?

Answer 10

there is limited supply of animal pancreas

continued possibility of allergic reactions to animal insulin

logic of using human protein if available

Question 11

What are the alternatives to insulin injections?

Answer 11

insulin pumps
- omnipod, Medtronic = continuous subcutaneous insulin infusion

inhaled insulin
- exubera = insulin is absorbed through the lung alveoli

buccal insulin
- oral-lyn (generex) = insulin is delivered to buccal mucosa

inhalation powder
- afrezza = dry powder formulation of recombinant human regular insulin

oral insulin
- emisphere
- nobex

Question 12

How does emisphere oral insulin work?
How does nobex oral insulin work?

Answer 12

emisphere
- carrier facilitates transport across membranes
- insulin dissociates from complex after transport

nobex
- covalent modification of insulin with oligomers at select sites facilitates transport across membranes

Question 13

Why are insulin lispro and insulin aspart given three times a day whereas insulin detemir and glargine are given once a day?

Answer 13

insulin lispro and insulin aspart
- peak action occurs within 30-60 minutes
- onset occurs within 10-15 minutes
- duration of action is 3-5 hours

insulin detemir and insulin glargine
- no peak
- duration of action is 24 hours
- insulin glargine microprecipitates after subcutaneous injection so it dissolves slowly to release insulin
- insulin detemir binds to albumin via a covalent link with a fatty acid chain to allow slow release