Summary
Highly sensitive procedures for the characterization of molecular species of insulin
in the circulation and for the isolation of the gene encoding human insulin have recently
been developed. Nine subjects with abnormal forms of insulin or proinsulin have been
reported. These include: [Leu B25 ], [Ser B24 ], [Leu A3 ] insulin as well as others that have not yet been identified.
The clinical syndrome associated with the secretion of an abnormal insulin or proinsulin
molecule presents with apparent endogenous insulin resistance with inappropriate high
levels of insulin for the prevailing blood glucose concentration and a high insulin/C-peptide
ratio due to the reduced catabolism of the abnormal insulin molecule. Diabetes occurs
if there is concomitant insulin resistance or pancreatic beta cell failure.
In addition, abnormal forms of insulin have been found in the insulin autoimmune syndrome
presenting with recurrent, self-limiting hypoglycemia. Abnormal insulin in the autoimmune
insulin syndrome suggests that abnormalities in endogenous antigens may be important
in the formation of antibodies in other autoimmune states. However, although abnormalities
in the insulin molecule may provoke the autoimmune response, it is also feasible that
the presence of antibodies to normal insulin and proinsulin in some way alters their
metabolism to yield abnormal products on high performance liquid chromatography (HPLC).
Abnormal forms of insulin have also been found in subjects with reactive hypoglycemia
and exogenous insulin-resistance and appear to be transmitted in an autosomal dominant
manner.
A protocol for the sequence of investigating subjects who potentially harbor a mutant
or otherwise abnormal form of insulin using HPLC and recombinant DNA technology is
presented.
Key-Words
Mutant Insulin
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Insulin Resistance
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Autoimmune
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Response
