Response of circulating immunoreactive somatostatin to nutritional stimuli in normal subjects

We have previously reported that in normal subjects plasma immunoreactive somatostatin levels rise after a mixed meal. The contribution of individual nutrients to this rise, and the molecular nature of the somatostatin immunoreactivity measured, have now been studied. Six normal healthy subjects received, on separate occasions, isocaloric (520 calories) and isovolumetric (260 ml) quantities of carbohydrate, protein, and fat. The mean fasting plasma somatostatin level was 29 +/- 5 pg/ml. After carbohydrate a peak of 48 +/- 7 pg/ml was reached at 30 min, and after protein and fat there were more sustained rises with peak levels of 74 +/- 8 pg/ml and 80 +/- 9 pg/ml, respectively. Sephadex G50 chromatography of extracts of fasting peripheral plasma showed two main peaks of somatostatin immunoreactivity, one coeluting with cyclic somatostatin and a larger peak of approximately 3500 molecular weight (mol wt). Levels of both 1600 and 35000 mol wt somatostatin were increased 60 min after a mixed meal. Approximately 80% of the 3500 mol wt form of somatostatin could be converted to the 1600 mol wt form by treatment with dithiothreitol (an agent which reduces disulphide bonds). It is concluded that: (a) in normal subjects fat and protein are potent stimuli for somatostatin release; (b) somatostatin in normal peripheral plasma exists in multiple forms, and that both 1600 and 35000 mol w forms of somatostatin immunoreactivity are stimulated by feeding; (c) the 3500 mol wt form could represent a dimer of somatostatin or a somatostatin molecule linked to a second peptide chain by disulphide bonds.