Glucagon secretion before and during arginine infusions was tested in 11 patients with diabetes associated with haemochromatosis. The results were compared with those obtained in six normal subjects and five patients with haemochromatosis but normal glucose tolerance. The patients with haemochromatosis, regardless of glucose tolerance, exhibited higer level of plasma immunoreactivity for glucagon (antiserum 30-K) suggesting hyperglucagonaemia. However, additional analysis revealed that a considerable amount of this glucagon immunoreactivity was due to cross-reacting material of high molecular weight, the levels of which were significantly higher in patients with idiopathic haemochromatosis. When this was deducted from the total immunoreactivity measured, the resulting values for true glucagon concentrations were similar to those of normal subjects. The data suggest that (1) patients with idiopathic haemochromatosis, whether or not associated with diabetes, exhibit plasma glucagon levels comparable with those of normal subjects; (2) the plasma of the same patients contains significantly more high-molecular-weight substances reacting with glucagon antiserum 30-K than is present in plasma of normal subjects; and (3) 'hyperglucagonaemia' may be erroneously suggested when glucagon is measured with certain antisera reputed to be specific for glucagon.
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