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I t has been found by Butterfield et al. [1] tha t Yguanidinobutyramide (HL-523), a compound with structural similarities to arginine and phenethylbiguanide, plays the role of a regulator in the metabolism of carbohydrates and proteins. This substance is an intermediary in the metabolism of arginine to GABA in bacteria; and the free acid appears in the urine of humans after meMs. From experiments carried out on humans and animals, it is known tha t y-guanidinobutyramide produces a significant decrease in the values of blood urea. This decrease is not related to any alteration in renal haemodynamics, but seems to derive from the urea cycle and the metabolism of the aminoacids. Equally, y-guanidinobutyramide produces very significant decreases of glyeaemia in experimental animals, which in some cases cause hypoglycaemic shock. The hypoglyeaemic effect is accompanied by a large glucose uptake by muscle, which leads us to the conclusion tha t under these experimental circumstances a secretion or release of insulin could have been produced. With the object of clarifying this possible effect, we have studied the action of y-guanidinobutyramide on the synthesis and release of insulin in vitro (secretion). For this we took advantage of an experimental turn into two others by a longitudinal cut, and a piece of each one of these sections was incubated in each vessel. Each vessel therefore contained a piece corresponding to the head of the pancreas and another to the taft. Since a spontaneous secretion of insulin occurs after the excision of the pancreas, the two vessels with the pieces of pancreas were incubated for an hour as a control in order to determine the extent of this spontaneous secretion. After this initiM incubation the pieces were placed into other vessels under the conditions to be described later on. The incubation media was Krebs-Ringer I I supplemented in all vessels with glucose (0.6 mg/ml), gelatine (0.6 mg/ml), sodium pyruvate (bmM[), sodium fumarate (bmM) and sodium glutamate (bmM). The incubation vessels used to s tudy the effect of 7-guanidinobutyramide (HL-523) contained this compound at a concentrat ion of 1 x 10-aM. Insulin was measured by the method of Hales and Randle [3]. The insulin in the pancreas was extracted and partially purified by the procedure of Coore and Randle [2]. Table 1 shows the values obtained for the secretion and synthesis of insulin using rabbi t pancreas in the absence or presence of y-guanidinobutyramide (1 X 10-%I).

The effect of ?-guanidinobutyramide on the secretion and synthesis of insulin in vitro