Insulins Flashcards
What is the main source of insulin?
Recombinant human insulin
-Plasmid is expressed in either E.coli or Transformed yeast (depending on company making it)
What are the advantages of using recombinant human insulin?
-No longer come from animal sources
-Pure (homogenous)
-Can control amino acid sequences (can make it rapid acting or slowly absorbed)
-Companies can produce large quantities of insulin
Is insulin absorbed well orally?
NO
-currently all forms of insulin available are injectable
Which forms of insulin have a VERY RAPID ONSET with a VERY SHORT ACTION?
-Lispro (Humalog)
-Aspart (Novolog)
-Glulisine (Apidra)
Which form of insulin has a RAPID ONSET with a SHORT ACTION?
Regular (R)
Which form of insulin has an INTERMEDIATE ONSET/ACTION
NPH (N)
Which forms of insulin have a SLOW ONSET with a LONG ACTION?
-Glargine (Lantus)
-Detemir (Levemir)
-Degludec (Tresiba)
How do the “lente” insulins work?
The insulin forms complexes with zinc to slow down its absorption
-the monomer is absorbed
Semilente: small particles, non-crystalline
Lente (L)- small particles, large crystalline complexes
Ultralente (U)- Only large crystalline complexes
(the bigger the complex, the slower the absorption and longer acting it is)
**NO LONGER USED THERAPEUTICALLY
What is the structure of the Insulin Hexamer Nucleated by Zinc?
Trimer of Dimers
Which of the insulins is NOT genetically modified?
NPH insulin
What is the structure of NPH insulin and how does this affect its absorption/duration of action?
-The insulin is bound to a protamine
- When it reaches the tissue, it must be released by proteases to form free insulin
*This insulin has:
–Slow Absorption
–Long Duration of Action
What is the structure of Lispro Insulin (Humalog) and how does this affect its absorption/duration of action?
-The positions of P28 (proline) and K29 (lysine) on the insulin beta chain are switched
-This prevents the dimer and hexamer formation typically seen in normal insulin
*This insulin has:
–Very Rapid Absorption
–Very Short Duration of Action
Which insulins should be injected immediately before meals?
-Lispro insulin (Humalog)
-Insulin Aspart (Novolog)
-Insulin Glulisine (Apidra)
When you want fast-acting insulin, what form should it be in?
The monomer form
When we want to interrupt dimerization of insulin, what part of the insulin structure do we target?
The beta chain
Which part of the insulin beta chain structure is important for complexing with zinc?
Histamine
What is the structure of Insulin Aspart (Novolog) and how does this affect its absorption/duration of action?
Proline 28 in the beta chain is changed to aspartate
-This disrupts dimerization of the insulin molecule
*This insulin has:
–Very Rapid Absorption
–Very Short Duration of Action
What is the structure of Insulin Glulisine (Apidra) and how does this affect its absorption/duration of action?
Asn 3 (asparagine) and Lys 29 (lysine) in the beta chain are switched to Lys (lysine) and Glu (Glutamic Acid)
-This disrupts dimerization of the insulin molecule
*This insulin has:
–Very Rapid Absorption
–Very Short Duration of Action
What is the structure of Insulin Glargine (Lantus) and how does this affect its absorption/duration of action?
–Asn 21 (asparagine) in the ALPHA chain is changed to Gly (Glycine)
–2 Arg (arginine) residues are added to the end of the BETA chain
-When injected, the pH is around 7.2-7.3
–Glargine is not soluble at this pH (Solution at pH of about 4)
–Therefore, glargine is slowly released from the injection site
*This insulin has:
–Slow Absorption
–Long Duration of Action
How long does it take for Glargine insulin (Lantus) to be absorbed?
24 hours
(Daily injection)
What is a benefit to using Insulin Glargine (Lantus) vs NPH insulin when it comes to glucose utilization?
NPH insulin shows a pronounced peak in glucose utilization right after the medication is injected
Insulin Glargine (Lantus) does not have a pronounced a peak in glucose utilization and, instead, shows steady usage over time
*We do not want a peak!
What is the structure of Insulin Detemir (Levemir) and how does it affect its absorption/duration of action?
Thr 30 (Threonine) is deleted in the beta chain and Lys 29 (Lysine) is myristylated (a fatty acid chain is attached)
-The fatty acid chain binds to serum albumin extensively
-The insulin is then slowly released from albumin over time
*This insulin has:
–Slow Absorption
–Long Duration of Action
How often does Insulin Detemir (Levemir) need to be injected?
Once or Twice daily
What is the structure of Insulin Degludec (Tresiba) and how does this affect its absorption/duration of action?
Thr (threonine) 30 in the beta chain is replaced by y-Glu/C16 fatty acid
–This fatty acid binds extensively to serum albumin
-The insulin is then slowly released from albumin over time
*This insulin has:
–Slow Absorption
–Long Duration of Action
