Human insulin immunogenicity

Human insulin, which is now less expensive than monospecies pork insulin and is also less immunogenic, has supplanted purified pork insulins. 

Human insulins appear to be as effective as—and considerably less immunogenic in diabetic patients than—beef-pork insulin mixtures and slightly less immunogenic than pork insulin. 

Fineberg SE, Galloway JA, Fineberg NS, Rathbun MJ, Hufferd S Immunogenicity of recombinant human insulin. Diabetolo-gia (1983) 25 465 69. 

Baker, R. S., Schmidtke, J. R., Ross, J. W., and Smith, W. C. (1981). Preliminary studies on the immunogenicity and amount of Escherichia coli polypeptides in biosynthetic human insulin produced by recombinant DNA technology. Lancet 2(8256), pp. 1139-1142. 

Human insulin is less immunogenic than bovine, but not porcine, insulin. When changing from animal to human insulin, patients taking <100 units of animal insulin are likely to require 10% less human insulin, and if taking >100 units animal insulin, 25% less human insulin. 

The long-term antigenicity of insulin lispro and crossreactivity with human insulin antibodies over 4 years has been investigated in 1221 patients with both type 1 and type 2 diabetes, either insulin-naive or with prior insulin treatment, in a multicenter combination of controlled and non-controlled open studies (30). Like recombinant human insulin, insulin lispro elicited a low immunogenic response. The reversal of amino acids in B28 and B29 is in a relatively non-immunogenic area. Moreover, antigenicity often correlates with residence of insulin in... 

Both pork and human insulin are definitively less immunogenic than beef insulin, producing fewer circulating insulin antibodies, but several studies have indicated no detectable change in antibody concentrations on switching from pork to human insulin or vice versa. Antibodies cause lipoatrophy and are responsible for the substantial insulin resistance seen in some patients, but both events are rare now that purified pork insulin is in common use. Interest has recently been revived in the possible contribution of antibodies in modifying metabolic control. In the short term and under hospital conditions, they are known to prolong the intravenous half-life of injected insulin and to delay the appearance in the circulation of a subcutaneously administered bolus dose. 

Ottesen JL, Nilsson P, Jami J, Welguny D, Duhrkop M, Bucchini D, Havelund S, Fogh JM.The potential immunogenicity of human insulin and insulin analogues evaluated in a transgenic mouse model. Diabetalogia 1994 37 1178-1185. 

Human insulin (humulin) is prepared by recombinant DNA technology or is synthesized from porcine insulin (enzymatic replacement of the terminal arginine with threonine). Human insulin is preferred to insulin prepared from animals because it is less antigenic. Porcine insulin differs from human insulin by one amino acid (terminal arginine). Bovine insulin is the most immunogenic preparation. A typical dosing... 

Schernthaner G (1993). Immunogenicity and allergenic potential of animal and human insulins. Diabetes Care. 16(suppl 3) 155-165. 

Studies in animals, healthy adults, and patients with type I diabetes mellitus have shown human insulin fo have pharmacologic effects identical to those of purified porcine insulin. A comparable pharmacokinetic profile also has been shown. Human insulin, however, administered intramuscularly or intravenously, may have a slightly faster onset and slightly shorter duration of action when compared with purified porcine insulin in patients with diabetes. The usual precautions concerning foxic potentials observed with insulin of animal origin should be followed with rDNA human insulin. As would be expected, the recombinant product has been shown fo be less immunogenic than animal insulins. 

Other mitogenicity in CHO-K1 and human BIO osteosarcoma cells, human hepatoma cells and MCF-7 cells to include drug binding study to IGF-1 and insulin receptors local tolerance in pigs immunogenicity studies in rabbits... 

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