Insulin

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Insulin

  1. 1. INSULIN : Structure  Computer-generated image of six insulin molecules assembled in a hexamer, highlighting the threefold symmetry, the zinc ions holding it together, and the histidine residues involved in zinc binding. Insulin is stored in the body as a hexamer, while the active form is the monomer.
  2. 2. SOURCES OF ANIMAL INSULIN Best sources : Cow and Pig Very small difference in the Pig -1 amino acid variation in B30 Cow insulin has two differences A8 and B30
  3. 3. Why Cow and Pig? Bovine Insulin Easy availability from slaughter houses Chicken and duck have 7 and 6 amino acid differences as compared to human insulin Hence, wouldn’t be good choices
  4. 4. Marketed product The first of these molecules to be marketed - called insulin lispro - is engineered such that lysine and proline resting on the C-terminal end of the B chain are reversed; this modification does not alter receptor binding, but minimizes the tendency to form dimmers and hexamers.
  5. 5. Importance of similarity The primary sequence of amino acids influences the tertiary structure of protein Hence, it’s possible that a change in the protein sequence could alter the tertiary structure Resulting in a different shape .
  6. 6. PI value of INSULIN The pi value for all animal insulins would be similar to human insulin (except for chicken and duck) This is because, amino acid changes all involved neutral amino acids. Chicken insulin would be more basic whereas duck would be more acidic.
  7. 7. Factors affecting Immune Response Insulin factorsPuritySpecies (bovine > pork > human)Physical properties (pH)Retarding agents (zinc, protamin, surfen) Individual factorsAgeImmunogenical background (HLA type)Presence of insulin autoantibodies Mode of insulin administrationSubcutaneous > intravenousInsulin pumpsInterrupted insulin therapy
  8. 8.  The amino acid sequence for insulin is almost the same in different mammals. Porcine insulin has only a single amino acid variation from the human variety, and bovine insulin varies by two amino acids. Both are active on the human receptor with approximately the same strength. Prior to the introduction of biosynthetic human insulin, insulin derived from sharks was widely used in Japan. Even insulin from some species of fish may be effective in humans. Non-human insulins can cause allergic reactions in a tiny number of people, as can genetically engineered "human" insulin
  9. 9. SDS-PAGE Electrophoresis ofInsulin and Proinsulin :-
  10. 10. OBSERVATIONS Proinsulin is a single stranded polypeptide with 3 intra-molecular disuphide bonds. Insulin is double-stranded polupeptide with 2 intermolecular and 1 intramolecular. In that case, there will be numerous A and B strands in solution and correct system AB system residue must find each other in solution before an intramolecular disulphide bond forms.
  11. 11. Insulin OVER Proinsulin! When insulin was originally purified from bovine or porcine pancreas, all the proinsulin was not fully removed. When some people used these insulins, the proinsulin may have caused the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin was injected.

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