First Glance

FAQ's
 
Human and Animal Insulin
 
What is major difference between human and animal insulin?
 
Animal and human insulins differ in structure. Both bovine and procine insulin differ from human insulin at the terminal amino acid of the B-chain. Bovine insulin differ procine insulin and human insulin at two more amino acids in the A-chain. These differences are in portions of the insulin molecule responsible for immunological response. Because of greater different in structure bovine insulin is much more immunogenic than human insulin, whereas porcine insulin is slightly more immunogenic than human insulin. Receptor binding areas of the insulin molecule show virtually no overlap with the areas responsible for the immunological responsible for the immunological response. Thus in the absence of antibody directed towards insulin, animal and human insulin would be expected to differ little in 'biological activity’. Circulating antibodies to insulin, if present, especially in high concentration; can result in less insulin being available for binding to cells, thereby reducing its effect.
 
Highly purified beef insulin, even if present in trace amounts enhances antibody formation to procine insulin.
 
How does ‘purity’ of an insulin affect its immunogenicity?
 
Early commercial insulin was a relatively impure product containing several non-insulin substances. Schlichtkrull and colleagues developed the first highly purified insulin around 1970, and refined it further to a single component insulin in 1972. The development of pure insulin was necessary before the inappropriateness of the use of less pure forms could be demonstrated.
 
As early as 1964 it had been reported that circulating insulin antibodies could be demonstrated in 97% of insulin-treated patients, while none were found in normal subjects or persons with diabetes who had not been given insulin. It was initially thought that the antigenicity was due to structural differences between animal and human insulin, but later experiments proven the highly purified insulin is less immunogenic than insulin of conventional grade purity, and human insulin is the least antigenic.
 
Are anti-insulin antibodies harmful?
 
In the past it had been suggested that insulin antibodies may cause immune complex disease, but this has not been substantiated. It has also been suggested that insulin antibodies may cross the placenta and be harmful to the foetus of the diabetic mother.
 
The main arguments against animal insulin have centered around the effect they may have on control of diabetes. It has been shown that in normal persons, insulin is secreted in sharp peaks in response to meal, and the aim of antidiabetic therapy should be to mimic this. It has been shown that in patients with anti-insulin antibodies, free insulin concentrations rise sluggishly, and this is one reason for the less than optimal effect of exogenously administered insulin in reversing plasma glucose excursions to normal in the management of the diabetic state.
 
In view of preventing or minimizing insulin antibody formation and development of later complications due to it, it is advisable to use the least immunogenic insulin viz. human insulin whenever insulin is to be administered intermittently e.g., during pregnancy, while treating acutely stressful states such as myocardial infarction, surgery, serious infection, etc. in the person with diabetes.
 
Why should human insulin be preferred whenever possible even in the daily management of diabetes?
 
Human insulin is preferred even for regular use whenever possible because of its lower innate immunogenicity than any animal insulin. With the introduction of human insulin in therapy there has been a great reduction in the reported incidence of local allergy at the injection site, generalized allergy, lipoatrophy, and lipodystrophy.
 
Human insulin is also preferable because its use has been shown to lead to a fall in anti-insulin antibody titre in persons previously treated with conventional animal insulin. This has been shown to result in a fall in insulin requirement and a simultaneous rise in free insulin levels in serum. This has led to the development of protocols of dose adjustment when changing over patients from conventional insulin to highly purified animal insulin and human insulin.
 

Human insulin is also be preferable because of its faster onset of action, which in turn may lead to better control of post-meal hyperglycemia than possible with animal insulin.

 
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