Radioimmunoassay of Plasma Pancreatic Glucagon, and Clinical and Experimental Investigations on Subjects with Diabetes Mellitus and Liver Disorders

Basic radioimmunoassay studies of pancreatic glucagon in plasma were carried out and the assay system thus obtained was used for the determination of plasma glucagon concentration in subjects with diabetes mellitus and liver disorder clinically and experimentally. The results obtained were as follows : 1) In order to obtain labelled glucagon with a minimal damaged fraction, it was noted that extremely mild labelling conditions were necessary. 2) Pure 125I-glucagon which satisfactorily bound to glucagon antibodies (30 K, Unger's Foundation) were obtained by repurification using microfine silica (Quso G-32). 3) A sensitive and reproducible radioimmunoassay (RIA) system was thus established by use of polyethyleneglycol for the separation of antibody-bound hormone from the free hormone. 4) The RIA system was applied to the examination of plasma glucagon, and significant elevations in the fasting state and higher reactive responses after administration of arginine were observed in patients with diabetes mellitus and with liver disorder, compared with those in normal controls. 5) Animal experiments were, at the same time, carried out on streptozotocin induced diabetic rats and rats with liver damage induced by CCｌ4 administration, and the same changes in plasma glucagon levels were found in these rats. Discussions were made on the mechanism of the abnormally increased plasma glucagon levels in fasting state and the hyperresponsiveness to arginine in subjects with diabetes mellitus and liver disorder