Npsc521P Lecture 45 Diabetes 1 Insulin Dependent

Front 1

1. Name the insulins that eliminated the problem of allergic reactions.

Back 1

• Insulin discovered 80 years ago from extract of pancreas of the dog
• Best and Banting, Un Toronto
• Early insulin preps from porcine and bovine sources had impurities to cause allergic reactions
• Up to 1980’s, insulin sources were porcine and bovine – induced allergic reactions
• In early 1980’s purified pork insulin and recombinant human insulin eliminated the allergy problem.

Front 2

2. Describe the chemical structure of insulin

Back 2

• A polypeptide with molecular weight of approx 5600 Daltons
• Stimulates anabolic processes in muscle, liver and fat cells
• Binds to cell-surface receptor to initiate signal propagation within the cell

Front 3

3. List the four regular insulin preparations and their onset and duration times.

Back 3

See Notes

Front 4

4. How does the human type insulin differ from the purified pork insulin?

Back 4

• Humulin (human insulin)
o recombinant DNA origin
o produced by Eli Lilly and Company
o identical to insulin produced by human pancreas
o contains no animal source pancreatic impurities that may contribute to allergic reactions

Front 5

5. List the limitations of the four standard insulins.

Back 5

• After injection, they all caused in some fashion hypoglycemia because they worked very efficiently upon onset
• As glycosylated hemoglobin values approached normal range, “they just kept working” to further reduce blood sugar.
• A “split-mix” regimen of NPH and regular insulin (70/30 mix respectively) used to this day was the best approach to provide both initial (after meals) and basal blood sugar control
• Diabetes experts suggested that insulin formulation had to more closely duplicate the basal and mealtime components of endogenous insulin secretion.

Front 6

6. For the insulin analogues lispro, aspart and glargine, describe the chemical differences to endogenous insulin.

Back 6

• Lispro
o Made from the inversion of the lysine of B29 and the proline of B28 of human insulin
o Results in a very rapid action upon injection the most closely resembles prandial insulin release
o Similar to insulin aspart in onset and duration of action
o Structure not available at time of this program
o Results in a very rapid action upon injection the most closely resembles prandial insulin release

• Aspart
o Proline at B28 replaced with the negatively charged aspartic acid
o Results in a very rapid action upon injection the most closely resembles prandial insulin release

• Glargine (long acting analog; brand name Lantus)
o A prolonged absorption after sc injection with no peak activity
o Produced by the substitution of glycine for asparagine at position A21 and the addition of two argine molecules at B30.

Front 7

7. Describe how the insulin analogues are used in diabetes.

Back 7

• Insulin analogue preps
o Had action profiles that afforded more flexible treatment regimens
o Had lower risk of developing hypoglycemia
• Used:
o Individually in type 1 diabetes better mimic endogenous insulin
o Together with oral drugs in type 2 diabetes i.e. Insulin lispro at mealtime enhances actions of the orals

Front 8

8. Define the preparation known as Novolog Mix 70/30 and its duration of action.

Back 8

• Premixed insulin analogues
o Brand name= Novolog Mix 70/30
 Insulin aspart protamine 70%
 Insulin aspart 30%
 A single injection with rapid onset like regular insulin, and then a duration similar to intermediate-acting insulins (12-18 hrs)

Front 9

9. For insulin detemir and insulin glulisine, define what they are chemically, their durations of action and how used in diabetes.

Back 9

• Insulin detemir
o A single amino acid omission (threonine at B 30) and addition of a 14 carbon fatty acid chain at B29
o Lower dose = 12-18 hours duration
o Higher dose = 24 hour duration
o Treatment of both type 1 diabetes and type 2 diabetes to improve glycemic control

• Insulin glulisine (Apidra)
o Replacement of two amino acids on the B chain (B3, B29)
o A rapid acting insulin analog (2-4 hours)
o Treatment of both type 1 diabetes and type 2 diabetes to improve glycemic control