Metabolism
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Was she murdered by insulin injection?
Key points from this exercise:
Excessive insulin, either as a result of an insulin secreting tumour or by injection can lead to profound hypoglycaemia.
Consumption of alcohol with a small amount of carbohydrate can lead to hypoglycaemia. Carbohydrate stimulates insulin secretion and alcohol suppresses gluconeogenesis.
Biological assay of insulin measures the stimulation of glucose metabolism in muscle tissue incubated with [14C]glucose in vitro; the rat diaphragm muscle is commonly used.
Radio-immunoassay of insulin measures its ability to bind to anti-insulin antibodies, in competition with radioactively labelled insulin. This method is rapid and a large number of samples can be assayed at the same time.
Insulin is measured in units of biological activity.
Insulin consists of two peptide chains (A and B) joined by disulphide bridges. However it is coded for by a single gene, and is synthesised as a single, larger peptide (prepro-insulin) with a signal sequence that is cleaved in the rough endoplasmic reticulum. The resultant pro-insulin undergoes further post-synthetic modification in the Golgi apparatus, removing the C-peptide that connects the A and B chains.
C-peptide is secreted together with insulin. It has no biological activity, but is useful in clinical chemistry because while insulin is cleared from the circulation within about 5 minutes, C-peptide survives for 15 - 30 minutes. Measurement of C-peptide gives a more reliable determination of the insulin response to aa test dose of carbohydrate.
There have been a number of murders and suspected murders associated with insulin, and many cases have been collected by Vincent Marks and Caroline Richmond in a book called Insulin Murders (RSM Press, 2007)