Protamine-insulin complex

Whereas extensive purification has resulted in a very pure and homogeneous insulin product, the protamine used for retardation in NPH type preparations (see Section 2.2.1) is highly inhomogeneous as it contains four major components, which are present in approximately equal amounts. AU four components show close structural homology with one another, and consequently they generate nearly identical protamine-insulin complexes (Hoffinaneta/., 1990). 

Protamine zinc insulin insulin complexed to excess protamine in order to prolong its duration of action... 

Intermediate-acting insulins are either the neutral protamine Hagedorn insulin (NPH isophane insulin suspension) or the Lente insulin (insulin zinc suspension) the former is a suspension of the insulin-protamine-zinc complex in a phosphate buffer and the latter is a mixture of crystallized and amorphous insulin in acetate buffer. These preparations have an onset of action within about 2h, peak activity after about 4-12 h, and a duration of up to 24 h (Table 4). Commercially available mixtures of soluble insulins and isophane insulins have activities that would normally place them within the intermediate-acting category. Mixed insulin-zinc suspensions are sometimes classified as either intermediate- or long-acting as the duration of action may be up to 30 h. 

Insulin complexed with zinc and protamine. This form of insulin has a slower onset and long duration. 

Di Abietes different preparations of insulin contain some insulin complexed with protamine that is absorbed slowly after injection. Protamine is a protein preparation from rainbow trout sperm containing arginine-rich peptides that bind insulin. Which of the following provides the best explanation for complex formation between protamine and insulin ... 

NPH Isophane Human Insulin Suspension. NPH isophane insulin, also called Humulin N, Insulatard NPH Human, or Novolin N is an intermediate-acting form of human insulin produced by recombinant DNA techniques. Mixtures Humulin 70/30 and Novolin 70/30 contain 70% NPH isophane and 30% regular, whereas Humulin 50/50 contains 50% NPH isophane and 50% regular. It is adrninistered subcutaneously and should not be given intravenously. Absorption is delayed because the insulin is conjugated with protamine in a complex of reduced isoelectric solubiUty. Therapeutically, this preparation is probably comparable to purified porcine NPH insulin. However, human NPH insulin may have a slightly shorter duration of action than comparable purified porcine products. 

Insulin suspensions. When the hormone is injected as a suspension of insulin-containing particles, its dissolution and release in subcutaneous tissue are retarded (rapid, intermediate, and slow insulins). Suitable particles can be obtained by precipitation of apolar, poorly water-soluble complexes consisting of anionic insulin and cationic partners, e.g the polycationic protein protamine or the compound aminoqui-nuride (Surfen). In the presence of zinc and acetate ions, insulin crystallizes crystal size determines the rate of dissolution. Intermediate insulin preparations (NPH or isophane, lente or zinc insulin) act for 18 to 26 h, slow preparations (protamine zinc insulin, ultralente or extended zinc insulin) for up to 36 h. 

This is due to delayed absorption of the insulin because of conjugation of the insulin with protamine to form a less soluble complex. The NPH should only be given subcutaneously (never IV), and is useful in treating all forms of diabetes except diabetic ketoacidosis or emergency hyperglycemia. 

Correct answer = C. Protamine complexes with insulin to form an insoluble complex that is slowly absorbed. Insulin is not administered orally because it is destroyed by proteases in the Gl tract. Diet therapy and/or sulfonylureas are often effective without additional insulin In the therapy of Type II diabetics. Ketoacidosis is the most life-threatening consequence of Type I diabetics and requires adequate treatment with insuiin, not sulfonylureas. Insulin acts by binding to specific receptors in the cell membrane, not in the nucleus. 

Zinc and protamine have been added to insulin to form complexes and control the duration of action. 

These interactions are always unwanted. A good example is the inappropriate mixing of insulins. Slower release insulins are complexed with protamine zinc in excess, while the conjugation of insulin with such adjuvant takes place slowly, especially in the relatively low temperature of a refrigerator. Drawing up the lente insulin first, and then sticking the needle into the soluble insulin,... 

Insulin is typically complexed with zinc and/or protamine, a charged protein. This complex -ing allows the hormone to be slowly dissociated from the complex, making the preparation longer-acting. 

NPH insulin is neutral protamine hagedorn insulin. It is complexed with protamine and is intermediate-acting. 

Identify the neutral protamine-complexed insulin (NPH insulin). 

Yip, C. M., Brader, M. L., Frank, B. H., DeFelippis, M. R., and Ward, M. D. 2000. Structural studies of a crystalline insulin analog complex with protamine by atomic force microscopy, Biophys J 78,466-473. 

Isophane insulins a range of insulins based on either human or porcine insulins is available in which protamine is added to produce between 50% and 85% complexation with the insulin. 

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